Cellular and Molecular Life Sciences

, Volume 75, Issue 9, pp 1587–1612 | Cite as

Diversity among POU transcription factors in chromatin recognition and cell fate reprogramming

Review
  • 423 Downloads

Abstract

The POU (Pit-Oct-Unc) protein family is an evolutionary ancient group of transcription factors (TFs) that bind specific DNA sequences to direct gene expression programs. The fundamental importance of POU TFs to orchestrate embryonic development and to direct cellular fate decisions is well established, but the molecular basis for this activity is insufficiently understood. POU TFs possess a bipartite ‘two-in-one’ DNA binding domain consisting of two independently folding structural units connected by a poorly conserved and flexible linker. Therefore, they represent a paradigmatic example to study the molecular basis for the functional versatility of TFs. Their modular architecture endows POU TFs with the capacity to accommodate alternative composite DNA sequences by adopting different quaternary structures. Moreover, associations with partner proteins crucially influence the selection of their DNA binding sites. The plentitude of DNA binding modes confers the ability to POU TFs to regulate distinct genes in the context of different cellular environments. Likewise, different binding modes of POU proteins to DNA could trigger alternative regulatory responses in the context of different genomic locations of the same cell. Prominent POU TFs such as Oct4, Brn2, Oct6 and Brn4 are not only essential regulators of development but have also been successfully employed to reprogram somatic cells to pluripotency and neural lineages. Here we review biochemical, structural, genomic and cellular reprogramming studies to examine how the ability of POU TFs to select regulatory DNA, alone or with partner factors, is tied to their capacity to epigenetically remodel chromatin and drive specific regulatory programs that give cells their identities.

Keywords

POU Transcriptional regulation Cellular reprogramming Pioneer TFs 

Notes

Acknowledgements

We thank Andrew Hutchins, Sergiy Velychko for discussions and Yogesh Srivastava for help with structural models. R.J. is supported by the Ministry of Science and Technology of China (2013DFE33080, 2016YFA0100700, 2017YFA0105103) by the National Natural Science Foundation of China (Grant No. 31471238), a 100 talent award of the Chinese Academy of Sciences and by a Science and Technology Planning Projects of Guangdong Province, China (2017B030314056 and 2016A050503038). V.M. thanks the CAS-TWAS (Chinese Academy of Sciences–The World Academy of Sciences) President’s Fellowship and UCAS (University of Chinese Academy of Science) for financial and infrastructure support.

References

  1. 1.
    Parslow TG, Blair DL, Murphy WJ, Granner DK (1984) Structure of the 5′ ends of immunoglobulin genes: a novel conserved sequence. Proc Natl Acad Sci USA 81(9):2650–2654PubMedPubMedCentralGoogle Scholar
  2. 2.
    Carbon P, Murgo S, Ebel JP, Krol A, Tebb G, Mattaj LW (1987) A common octamer motif binding protein is involved in the transcription of U6 snRNA by RNA polymerase III and U2 snRNA by RNA polymerase II. Cell 51(1):71–79PubMedGoogle Scholar
  3. 3.
    LaBella F, Sive HL, Roeder RG, Heintz N (1988) Cell-cycle regulation of a human histone H2b gene is mediated by the H2b subtype-specific consensus element. Genes Dev 2(1):32–39PubMedGoogle Scholar
  4. 4.
    Pruijn GJ, van Driel W, van der Vliet PC (1986) Nuclear factor III, a novel sequence-specific DNA-binding protein from HeLa cells stimulating adenovirus DNA replication. Nature 322(6080):656–659.  https://doi.org/10.1038/322656a0 PubMedGoogle Scholar
  5. 5.
    Sturm R, Baumruker T, Franza BR Jr, Herr W (1987) A 100-kD HeLa cell octamer binding protein (OBP100) interacts differently with two separate octamer-related sequences within the SV40 enhancer. Genes Dev 1(10):1147–1160PubMedGoogle Scholar
  6. 6.
    Staudt LM, Singh H, Sen R, Wirth T, Sharp PA, Baltimore D (1986) A lymphoid-specific protein binding to the octamer motif of immunoglobulin genes. Nature 323(6089):640–643.  https://doi.org/10.1038/323640a0 PubMedGoogle Scholar
  7. 7.
    Fletcher C, Heintz N, Roeder RG (1987) Purification and characterization of OTF-1, a transcription factor regulating cell cycle expression of a human histone H2b gene. Cell 51(5):773–781PubMedGoogle Scholar
  8. 8.
    Hanke JH, Landolfi NF, Tucker PW, Capra JD (1988) Identification of murine nuclear proteins that bind to the conserved octamer sequence of the immunoglobulin promoter region. Proc Natl Acad Sci USA 85(10):3560–3564PubMedPubMedCentralGoogle Scholar
  9. 9.
    Scheidereit C, Heguy A, Roeder RG (1987) Identification and purification of a human lymphoid-specific octamer-binding protein (OTF-2) that activates transcription of an immunoglobulin promoter in vitro. Cell 51(5):783–793PubMedGoogle Scholar
  10. 10.
    O’Neill EA, Kelly TJ (1988) Purification and characterization of nuclear factor III (origin recognition protein C), a sequence-specific DNA binding protein required for efficient initiation of adenovirus DNA replication. J Biol Chem 263(2):931–937PubMedGoogle Scholar
  11. 11.
    Clerc RG, Corcoran LM, LeBowitz JH, Baltimore D, Sharp PA (1988) The B-cell-specific Oct-2 protein contains POU box- and homeo box-type domains. Genes Dev 2(12A):1570–1581PubMedGoogle Scholar
  12. 12.
    Ko HS, Fast P, McBride W, Staudt LM (1988) A human protein specific for the immunoglobulin octamer DNA motif contains a functional homeobox domain. Cell 55(1):135–144PubMedGoogle Scholar
  13. 13.
    Muller MM, Ruppert S, Schaffner W, Matthias P (1988) A cloned octamer transcription factor stimulates transcription from lymphoid-specific promoters in non-B cells. Nature 336(6199):544–551.  https://doi.org/10.1038/336544a0 PubMedGoogle Scholar
  14. 14.
    Scheidereit C, Cromlish JA, Gerster T, Kawakami K, Balmaceda CG, Currie RA, Roeder RG (1988) A human lymphoid-specific transcription factor that activates immunoglobulin genes is a homoeobox protein. Nature 336(6199):551–557.  https://doi.org/10.1038/336551a0 PubMedGoogle Scholar
  15. 15.
    Bodner M, Castrillo JL, Theill LE, Deerinck T, Ellisman M, Karin M (1988) The pituitary-specific transcription factor GHF-1 is a homeobox-containing protein. Cell 55(3):505–518PubMedGoogle Scholar
  16. 16.
    Ingraham HA, Chen RP, Mangalam HJ, Elsholtz HP, Flynn SE, Lin CR, Simmons DM, Swanson L, Rosenfeld MG (1988) A tissue-specific transcription factor containing a homeodomain specifies a pituitary phenotype. Cell 55(3):519–529PubMedGoogle Scholar
  17. 17.
    Finney M, Ruvkun G, Horvitz HR (1988) The C. elegans cell lineage and differentiation gene unc-86 encodes a protein with a homeodomain and extended similarity to transcription factors. Cell 55(5):757–769PubMedGoogle Scholar
  18. 18.
    Herr W, Sturm RA, Clerc RG, Corcoran LM, Baltimore D, Sharp PA, Ingraham HA, Rosenfeld MG, Finney M, Ruvkun G et al (1988) The POU domain: a large conserved region in the mammalian pit-1, oct-1, oct-2, and Caenorhabditis elegans unc-86 gene products. Genes Dev 2(12A):1513–1516PubMedGoogle Scholar
  19. 19.
    McGinnis W, Garber RL, Wirz J, Kuroiwa A, Gehring WJ (1984) A homologous protein-coding sequence in Drosophila homeotic genes and its conservation in other metazoans. Cell 37(2):403–408PubMedGoogle Scholar
  20. 20.
    Scott MP, Weiner AJ (1984) Structural relationships among genes that control development: sequence homology between the Antennapedia, Ultrabithorax, and fushi tarazu loci of Drosophila. Proc Natl Acad Sci USA 81(13):4115–4119PubMedPubMedCentralGoogle Scholar
  21. 21.
    Robertson M (1988) Homoeo boxes, POU proteins and the limits to promiscuity. Nature 336(6199):522–524.  https://doi.org/10.1038/336522a0 PubMedGoogle Scholar
  22. 22.
    Herr W, Cleary MA (1995) The POU domain: versatility in transcriptional regulation by a flexible two-in-one DNA-binding domain. Genes Dev 9(14):1679–1693PubMedGoogle Scholar
  23. 23.
    Jerabek S, Merino F, Scholer HR, Cojocaru V (2014) OCT4: dynamic DNA binding pioneers stem cell pluripotency. Biochim Biophys Acta 1839(3):138–154.  https://doi.org/10.1016/j.bbagrm.2013.10.001 PubMedGoogle Scholar
  24. 24.
    Phillips K, Luisi B (2000) The virtuoso of versatility: POU proteins that flex to fit. J Mol Biol 302(5):1023–1039.  https://doi.org/10.1006/jmbi.2000.4107 PubMedGoogle Scholar
  25. 25.
    Remenyi A, Tomilin A, Scholer HR, Wilmanns M (2002) Differential activity by DNA-induced quarternary structures of POU transcription factors. Biochem Pharmacol 64(5–6):979–984PubMedGoogle Scholar
  26. 26.
    Ryan AK, Rosenfeld MG (1997) POU domain family values: flexibility, partnerships, and developmental codes. Genes Dev 11(10):1207–1225PubMedGoogle Scholar
  27. 27.
    Tantin D (2013) Oct transcription factors in development and stem cells: insights and mechanisms. Development 140(14):2857–2866.  https://doi.org/10.1242/dev.095927 PubMedPubMedCentralGoogle Scholar
  28. 28.
    Verrijzer CP, Van der Vliet PC (1993) POU domain transcription factors. Biochim Biophys Acta 1173(1):1–21PubMedGoogle Scholar
  29. 29.
    Wegner M, Drolet DW, Rosenfeld MG (1993) POU-domain proteins: structure and function of developmental regulators. Curr Opin Cell Biol 5(3):488–498PubMedGoogle Scholar
  30. 30.
    Gold DA, Gates RD, Jacobs DK (2014) The early expansion and evolutionary dynamics of POU class genes. Mol Biol Evol 31(12):3136–3147.  https://doi.org/10.1093/molbev/msu243 PubMedPubMedCentralGoogle Scholar
  31. 31.
    Rosenfeld MG (1991) POU-domain transcription factors: pou-er-ful developmental regulators. Genes Dev 5(6):897–907PubMedGoogle Scholar
  32. 32.
    Holland PW, Booth HA, Bruford EA (2007) Classification and nomenclature of all human homeobox genes. BMC Biol 5:47.  https://doi.org/10.1186/1741-7007-5-47 PubMedPubMedCentralGoogle Scholar
  33. 33.
    Scholer HR (1991) Octamania: the POU factors in murine development. Trends Genet 7(10):323–329PubMedGoogle Scholar
  34. 34.
    Hutchins AP, Yang Z, Li Y, He F, Fu X, Wang X, Li D, Liu K, He J, Wang Y, Chen J, Esteban MA, Pei D (2017) Models of global gene expression define major domains of cell type and tissue identity. Nucleic Acids Res 45(5):2354–2367.  https://doi.org/10.1093/nar/gkx054 PubMedPubMedCentralGoogle Scholar
  35. 35.
    Sturm RA, Das G, Herr W (1988) The ubiquitous octamer-binding protein Oct-1 contains a POU domain with a homeo box subdomain. Genes Dev 2(12A):1582–1599PubMedGoogle Scholar
  36. 36.
    Landolfi NF, Capra JD, Tucker PW (1986) Interaction of cell-type-specific nuclear proteins with immunoglobulin VH promoter region sequences. Nature 323(6088):548–551.  https://doi.org/10.1038/323548a0 PubMedGoogle Scholar
  37. 37.
    Staudt LM, Clerc RG, Singh H, LeBowitz JH, Sharp PA, Baltimore D (1988) Cloning of a lymphoid-specific cDNA encoding a protein binding the regulatory octamer DNA motif. Science 241(4865):577–580PubMedGoogle Scholar
  38. 38.
    Andersen B, Weinberg WC, Rennekampff O, McEvilly RJ, Bermingham JR Jr, Hooshmand F, Vasilyev V, Hansbrough JF, Pittelkow MR, Yuspa SH, Rosenfeld MG (1997) Functions of the POU domain genes Skn-1a/i and Tst-1/Oct-6/SCIP in epidermal differentiation. Genes Dev 11(14):1873–1884PubMedGoogle Scholar
  39. 39.
    Matsumoto I, Ohmoto M, Narukawa M, Yoshihara Y, Abe K (2011) Skn-1a (Pou2f3) specifies taste receptor cell lineage. Nat Neurosci 14(6):685–687.  https://doi.org/10.1038/nn.2820 PubMedPubMedCentralGoogle Scholar
  40. 40.
    Andersen B, Schonemann MD, Pearse RV 2nd, Jenne K, Sugarman J, Rosenfeld MG (1993) Brn-5 is a divergent POU domain factor highly expressed in layer IV of the neocortex. J Biol Chem 268(31):23390–23398PubMedGoogle Scholar
  41. 41.
    He X, Treacy MN, Simmons DM, Ingraham HA, Swanson LW, Rosenfeld MG (1989) Expression of a large family of POU-domain regulatory genes in mammalian brain development. Nature 340(6228):35–41.  https://doi.org/10.1038/340035a0 PubMedGoogle Scholar
  42. 42.
    Mathis JM, Simmons DM, He X, Swanson LW, Rosenfeld MG (1992) Brain 4: a novel mammalian POU domain transcription factor exhibiting restricted brain-specific expression. EMBO J 11(7):2551–2561PubMedPubMedCentralGoogle Scholar
  43. 43.
    Wey E, Lyons GE, Schafer BW (1994) A human POU domain gene, mPOU, is expressed in developing brain and specific adult tissues. Eur J Biochem 220(3):753–762PubMedGoogle Scholar
  44. 44.
    Monuki ES, Weinmaster G, Kuhn R, Lemke G (1989) SCIP: a glial POU domain gene regulated by cyclic AMP. Neuron 3(6):783–793PubMedGoogle Scholar
  45. 45.
    Suzuki N, Rohdewohld H, Neuman T, Gruss P, Scholer HR (1990) Oct-6: a POU transcription factor expressed in embryonal stem cells and in the developing brain. EMBO J 9(11):3723–3732PubMedPubMedCentralGoogle Scholar
  46. 46.
    Nakai S, Kawano H, Yudate T, Nishi M, Kuno J, Nagata A, Jishage K, Hamada H, Fujii H, Kawamura K et al (1995) The POU domain transcription factor Brn-2 is required for the determination of specific neuronal lineages in the hypothalamus of the mouse. Genes Dev 9(24):3109–3121PubMedGoogle Scholar
  47. 47.
    Schonemann MD, Ryan AK, McEvilly RJ, O’Connell SM, Arias CA, Kalla KA, Li P, Sawchenko PE, Rosenfeld MG (1995) Development and survival of the endocrine hypothalamus and posterior pituitary gland requires the neuronal POU domain factor Brn-2. Genes Dev 9(24):3122–3135PubMedGoogle Scholar
  48. 48.
    Scholer HR, Hatzopoulos AK, Balling R, Suzuki N, Gruss P (1989) A family of octamer-specific proteins present during mouse embryogenesis: evidence for germline-specific expression of an Oct factor. EMBO J 8(9):2543–2550PubMedPubMedCentralGoogle Scholar
  49. 49.
    Schreiber E, Harshman K, Kemler I, Malipiero U, Schaffner W, Fontana A (1990) Astrocytes and glioblastoma cells express novel octamer-DNA binding proteins distinct from the ubiquitous Oct-1 and B cell type Oct-2 proteins. Nucleic Acids Res 18(18):5495–5503PubMedPubMedCentralGoogle Scholar
  50. 50.
    Gerrero MR, McEvilly RJ, Turner E, Lin CR, O’Connell S, Jenne KJ, Hobbs MV, Rosenfeld MG (1993) Brn-3.0: a POU-domain protein expressed in the sensory, immune, and endocrine systems that functions on elements distinct from known octamer motifs. Proc Natl Acad Sci USA 90(22):10841–10845PubMedPubMedCentralGoogle Scholar
  51. 51.
    Lillycrop KA, Budrahan VS, Lakin ND, Terrenghi G, Wood JN, Polak JM, Latchman DS (1992) A novel POU family transcription factor is closely related to Brn-3 but has a distinct expression pattern in neuronal cells. Nucleic Acids Res 20(19):5093–5096PubMedPubMedCentralGoogle Scholar
  52. 52.
    Turner EE, Jenne KJ, Rosenfeld MG (1994) Brn-3.2: a Brn-3-related transcription factor with distinctive central nervous system expression and regulation by retinoic acid. Neuron 12(1):205–218PubMedGoogle Scholar
  53. 53.
    Xiang M, Zhou L, Peng YW, Eddy RL, Shows TB, Nathans J (1993) Brn-3b: a POU domain gene expressed in a subset of retinal ganglion cells. Neuron 11(4):689–701PubMedGoogle Scholar
  54. 54.
    Ninkina NN, Stevens GE, Wood JN, Richardson WD (1993) A novel Brn3-like POU transcription factor expressed in subsets of rat sensory and spinal cord neurons. Nucleic Acids Res 21(14):3175–3182PubMedPubMedCentralGoogle Scholar
  55. 55.
    Zhou H, Yoshioka T, Nathans J (1996) Retina-derived POU-domain factor-1: a complex POU-domain gene implicated in the development of retinal ganglion and amacrine cells. J Neurosci 16(7):2261–2274PubMedGoogle Scholar
  56. 56.
    Lenardo MJ, Staudt L, Robbins P, Kuang A, Mulligan RC, Baltimore D (1989) Repression of the IgH enhancer in teratocarcinoma cells associated with a novel octamer factor. Science 243(4890):544–546PubMedGoogle Scholar
  57. 57.
    Okamoto KOH, Okuda A, Sakai M, Muramatsu M, Hamada H (1990) A novel octamer binding transcription factor is differentially expressed in mouse embryonic cells. Cell 60(3):461–472.  https://doi.org/10.1016/0092-8674(90)90597-8 PubMedGoogle Scholar
  58. 58.
    Scholer HR, Ruppert S, Suzuki N, Chowdhury K, Gruss P (1990) New type of POU domain in germ line-specific protein Oct-4. Nature 344(6265):435–439.  https://doi.org/10.1038/344435a0 PubMedGoogle Scholar
  59. 59.
    Nichols J, Zevnik B, Anastassiadis K, Niwa H, Klewe-Nebenius D, Chambers I, Scholer H, Smith A (1998) Formation of pluripotent stem cells in the mammalian embryo depends on the POU transcription factor Oct4. Cell 95(3):379–391PubMedGoogle Scholar
  60. 60.
    Niwa H, Miyazaki J, Smith AG (2000) Quantitative expression of Oct-3/4 defines differentiation, dedifferentiation or self-renewal of ES cells. Nat Genet 24(4):372–376.  https://doi.org/10.1038/74199 PubMedGoogle Scholar
  61. 61.
    Yuan H, Corbi N, Basilico C, Dailey L (1995) Developmental-specific activity of the FGF-4 enhancer requires the synergistic action of Sox2 and Oct-3. Genes Dev 9(21):2635–2645PubMedGoogle Scholar
  62. 62.
    Takeda J, Seino S, Bell GI (1992) Human Oct3 gene family: cDNA sequences, alternative splicing, gene organization, chromosomal location, and expression at low levels in adult tissues. Nucleic Acids Res 20(17):4613–4620PubMedPubMedCentralGoogle Scholar
  63. 63.
    Mizuno N, Kosaka M (2008) Novel variants of Oct-3/4 gene expressed in mouse somatic cells. J Biol Chem 283(45):30997–31004.  https://doi.org/10.1074/jbc.M802992200 PubMedPubMedCentralGoogle Scholar
  64. 64.
    Lee J, Kim HK, Rho JY, Han YM, Kim J (2006) The human OCT-4 isoforms differ in their ability to confer self-renewal. J Biol Chem 281(44):33554–33565.  https://doi.org/10.1074/jbc.M603937200 PubMedGoogle Scholar
  65. 65.
    Atlasi Y, Mowla SJ, Ziaee SA, Gokhale PJ, Andrews PW (2008) OCT4 spliced variants are differentially expressed in human pluripotent and nonpluripotent cells. Stem Cells 26(12):3068–3074.  https://doi.org/10.1634/stemcells.2008-0530 PubMedGoogle Scholar
  66. 66.
    Andersen B, Pearse RV 2nd, Schlegel PN, Cichon Z, Schonemann MD, Bardin CW, Rosenfeld MG (1993) Sperm 1: a POU-domain gene transiently expressed immediately before meiosis I in the male germ cell. Proc Natl Acad Sci USA 90(23):11084–11088PubMedPubMedCentralGoogle Scholar
  67. 67.
    Pearse RV 2nd, Drolet DW, Kalla KA, Hooshmand F, Bermingham JR Jr, Rosenfeld MG (1997) Reduced fertility in mice deficient for the POU protein sperm-1. Proc Natl Acad Sci USA 94(14):7555–7560PubMedPubMedCentralGoogle Scholar
  68. 68.
    Frankenberg SR, Frank D, Harland R, Johnson AD, Nichols J, Niwa H, Scholer HR, Tanaka E, Wylie C, Brickman JM (2014) The POU-er of gene nomenclature. Development 141(15):2921–2923.  https://doi.org/10.1242/dev.108407 PubMedGoogle Scholar
  69. 69.
    Takeda H, Matsuzaki T, Oki T, Miyagawa T, Amanuma H (1994) A novel POU domain gene, zebrafish pou2: expression and roles of two alternatively spliced twin products in early development. Genes Dev 8(1):45–59PubMedGoogle Scholar
  70. 70.
    Weintraub H, Tapscott SJ, Davis RL, Thayer MJ, Adam MA, Lassar AB, Miller AD (1989) Activation of muscle-specific genes in pigment, nerve, fat, liver, and fibroblast cell lines by forced expression of MyoD. Proc Natl Acad Sci USA 86(14):5434–5438PubMedPubMedCentralGoogle Scholar
  71. 71.
    Xie H, Ye M, Feng R, Graf T (2004) Stepwise reprogramming of B cells into macrophages. Cell 117(5):663–676PubMedGoogle Scholar
  72. 72.
    Takahashi K, Tanabe K, Ohnuki M, Narita M, Ichisaka T, Tomoda K, Yamanaka S (2007) Induction of pluripotent stem cells from adult human fibroblasts by defined factors. Cell 131(5):861–872.  https://doi.org/10.1016/j.cell.2007.11.019 PubMedGoogle Scholar
  73. 73.
    Takahashi K, Yamanaka S (2006) Induction of pluripotent stem cells from mouse embryonic and adult fibroblast cultures by defined factors. Cell 126(4):663–676.  https://doi.org/10.1016/j.cell.2006.07.024 PubMedGoogle Scholar
  74. 74.
    Yu J, Vodyanik MA, Smuga-Otto K, Antosiewicz-Bourget J, Frane JL, Tian S, Nie J, Jonsdottir GA, Ruotti V, Stewart R, Slukvin II, Thomson JA (2007) Induced pluripotent stem cell lines derived from human somatic cells. Science 318(5858):1917–1920.  https://doi.org/10.1126/science.1151526 PubMedGoogle Scholar
  75. 75.
    Bar-Nur O, Verheul C, Sommer AG, Brumbaugh J, Schwarz BA, Lipchina I, Huebner AJ, Mostoslavsky G, Hochedlinger K (2015) Lineage conversion induced by pluripotency factors involves transient passage through an iPSC stage. Nat Biotechnol 33(7):761–768.  https://doi.org/10.1038/nbt.3247 PubMedPubMedCentralGoogle Scholar
  76. 76.
    Han DW, Tapia N, Hermann A, Hemmer K, Hoing S, Arauzo-Bravo MJ, Zaehres H, Wu G, Frank S, Moritz S, Greber B, Yang JH, Lee HT, Schwamborn JC, Storch A, Scholer HR (2012) Direct reprogramming of fibroblasts into neural stem cells by defined factors. Cell Stem Cell 10(4):465–472.  https://doi.org/10.1016/j.stem.2012.02.021 PubMedGoogle Scholar
  77. 77.
    Kim J, Efe JA, Zhu S, Talantova M, Yuan X, Wang S, Lipton SA, Zhang K, Ding S (2011) Direct reprogramming of mouse fibroblasts to neural progenitors. Proc Natl Acad Sci USA 108(19):7838–7843.  https://doi.org/10.1073/pnas.1103113108 PubMedPubMedCentralGoogle Scholar
  78. 78.
    Lujan E, Chanda S, Ahlenius H, Sudhof TC, Wernig M (2012) Direct conversion of mouse fibroblasts to self-renewing, tripotent neural precursor cells. Proc Natl Acad Sci USA 109(7):2527–2532.  https://doi.org/10.1073/pnas.1121003109 PubMedPubMedCentralGoogle Scholar
  79. 79.
    Thier M, Worsdorfer P, Lakes YB, Gorris R, Herms S, Opitz T, Seiferling D, Quandel T, Hoffmann P, Nothen MM, Brustle O, Edenhofer F (2012) Direct conversion of fibroblasts into stably expandable neural stem cells. Cell Stem Cell 10(4):473–479.  https://doi.org/10.1016/j.stem.2012.03.003 PubMedGoogle Scholar
  80. 80.
    Zhu S, Ambasudhan R, Sun W, Kim HJ, Talantova M, Wang X, Zhang M, Zhang Y, Laurent T, Parker J, Kim HS, Zaremba JD, Saleem S, Sanz-Blasco S, Masliah E, McKercher SR, Cho YS, Lipton SA, Kim J, Ding S (2014) Small molecules enable OCT4-mediated direct reprogramming into expandable human neural stem cells. Cell Res 24(1):126–129.  https://doi.org/10.1038/cr.2013.156 PubMedGoogle Scholar
  81. 81.
    Ambasudhan R, Talantova M, Coleman R, Yuan X, Zhu S, Lipton SA, Ding S (2011) Direct reprogramming of adult human fibroblasts to functional neurons under defined conditions. Cell Stem Cell 9(2):113–118.  https://doi.org/10.1016/j.stem.2011.07.002 PubMedPubMedCentralGoogle Scholar
  82. 82.
    Pang ZP, Yang N, Vierbuchen T, Ostermeier A, Fuentes DR, Yang TQ, Citri A, Sebastiano V, Marro S, Sudhof TC, Wernig M (2011) Induction of human neuronal cells by defined transcription factors. Nature 476(7359):220–223.  https://doi.org/10.1038/nature10202 PubMedPubMedCentralGoogle Scholar
  83. 83.
    Vierbuchen T, Ostermeier A, Pang ZP, Kokubu Y, Sudhof TC, Wernig M (2010) Direct conversion of fibroblasts to functional neurons by defined factors. Nature 463(7284):1035–1041.  https://doi.org/10.1038/nature08797 PubMedPubMedCentralGoogle Scholar
  84. 84.
    Wang H, Cao N, Spencer CI, Nie B, Ma T, Xu T, Zhang Y, Wang X, Srivastava D, Ding S (2014) Small molecules enable cardiac reprogramming of mouse fibroblasts with a single factor, Oct4. Cell Rep 6(5):951–960.  https://doi.org/10.1016/j.celrep.2014.01.038 PubMedPubMedCentralGoogle Scholar
  85. 85.
    Wapinski OL, Vierbuchen T, Qu K, Lee QY, Chanda S, Fuentes DR, Giresi PG, Ng YH, Marro S, Neff NF, Drechsel D, Martynoga B, Castro DS, Webb AE, Sudhof TC, Brunet A, Guillemot F, Chang HY, Wernig M (2013) Hierarchical mechanisms for direct reprogramming of fibroblasts to neurons. Cell 155(3):621–635.  https://doi.org/10.1016/j.cell.2013.09.028 PubMedGoogle Scholar
  86. 86.
    Nakagawa M, Koyanagi M, Tanabe K, Takahashi K, Ichisaka T, Aoi T, Okita K, Mochiduki Y, Takizawa N, Yamanaka S (2008) Generation of induced pluripotent stem cells without Myc from mouse and human fibroblasts. Nat Biotechnol 26(1):101–106.  https://doi.org/10.1038/nbt1374 PubMedGoogle Scholar
  87. 87.
    Jerabek S, Ng CK, Wu G, Arauzo-Bravo MJ, Kim KP, Esch D, Malik V, Chen Y, Velychko S, MacCarthy CM, Yang X, Cojocaru V, Scholer HR, Jauch R (2017) Changing POU dimerization preferences converts Oct6 into a pluripotency inducer. EMBO Rep 18(2):319–333.  https://doi.org/10.15252/embr.201642958 PubMedGoogle Scholar
  88. 88.
    Kim JB, Greber B, Arauzo-Bravo MJ, Meyer J, Park KI, Zaehres H, Scholer HR (2009) Direct reprogramming of human neural stem cells by OCT4. Nature 461(7264):649–653.  https://doi.org/10.1038/nature08436 PubMedGoogle Scholar
  89. 89.
    Kim JB, Sebastiano V, Wu G, Arauzo-Bravo MJ, Sasse P, Gentile L, Ko K, Ruau D, Ehrich M, van den Boom D, Meyer J, Hubner K, Bernemann C, Ortmeier C, Zenke M, Fleischmann BK, Zaehres H, Scholer HR (2009) Oct4-induced pluripotency in adult neural stem cells. Cell 136(3):411–419.  https://doi.org/10.1016/j.cell.2009.01.023 PubMedGoogle Scholar
  90. 90.
    Ebert AD, Yu J, Rose FF Jr, Mattis VB, Lorson CL, Thomson JA, Svendsen CN (2009) Induced pluripotent stem cells from a spinal muscular atrophy patient. Nature 457(7227):277–280.  https://doi.org/10.1038/nature07677 PubMedGoogle Scholar
  91. 91.
    Lee G, Papapetrou EP, Kim H, Chambers SM, Tomishima MJ, Fasano CA, Ganat YM, Menon J, Shimizu F, Viale A, Tabar V, Sadelain M, Studer L (2009) Modelling pathogenesis and treatment of familial dysautonomia using patient-specific iPSCs. Nature 461(7262):402–406.  https://doi.org/10.1038/nature08320 PubMedPubMedCentralGoogle Scholar
  92. 92.
    Dimos JT, Rodolfa KT, Niakan KK, Weisenthal LM, Mitsumoto H, Chung W, Croft GF, Saphier G, Leibel R, Goland R, Wichterle H, Henderson CE, Eggan K (2008) Induced pluripotent stem cells generated from patients with ALS can be differentiated into motor neurons. Science 321(5893):1218–1221.  https://doi.org/10.1126/science.1158799 PubMedGoogle Scholar
  93. 93.
    Soldner F, Hockemeyer D, Beard C, Gao Q, Bell GW, Cook EG, Hargus G, Blak A, Cooper O, Mitalipova M, Isacson O, Jaenisch R (2009) Parkinson’s disease patient-derived induced pluripotent stem cells free of viral reprogramming factors. Cell 136(5):964–977.  https://doi.org/10.1016/j.cell.2009.02.013 PubMedPubMedCentralGoogle Scholar
  94. 94.
    Park IH, Arora N, Huo H, Maherali N, Ahfeldt T, Shimamura A, Lensch MW, Cowan C, Hochedlinger K, Daley GQ (2008) Disease-specific induced pluripotent stem cells. Cell 134(5):877–886.  https://doi.org/10.1016/j.cell.2008.07.041 PubMedPubMedCentralGoogle Scholar
  95. 95.
    Zhou T, Benda C, Dunzinger S, Huang Y, Ho JC, Yang J, Wang Y, Zhang Y, Zhuang Q, Li Y, Bao X, Tse HF, Grillari J, Grillari-Voglauer R, Pei D, Esteban MA (2012) Generation of human induced pluripotent stem cells from urine samples. Nat Protoc 7(12):2080–2089.  https://doi.org/10.1038/nprot.2012.115 PubMedGoogle Scholar
  96. 96.
    Lujan E, Wernig M (2012) The many roads to Rome: induction of neural precursor cells from fibroblasts. Curr Opin Genet Dev 22(5):517–522.  https://doi.org/10.1016/j.gde.2012.07.002 PubMedPubMedCentralGoogle Scholar
  97. 97.
    Lin C, Yu C, Ding S (2013) Toward directed reprogramming through exogenous factors. Curr Opin Genet Dev 23(5):519–525.  https://doi.org/10.1016/j.gde.2013.06.002 PubMedPubMedCentralGoogle Scholar
  98. 98.
    Yu C, Liu K, Tang S, Ding S (2014) Chemical approaches to cell reprogramming. Curr Opin Genet Dev 28:50–56.  https://doi.org/10.1016/j.gde.2014.09.006 PubMedPubMedCentralGoogle Scholar
  99. 99.
    Li K, Zhu S, Russ HA, Xu S, Xu T, Zhang Y, Ma T, Hebrok M, Ding S (2014) Small molecules facilitate the reprogramming of mouse fibroblasts into pancreatic lineages. Cell Stem Cell 14(2):228–236.  https://doi.org/10.1016/j.stem.2014.01.006 PubMedPubMedCentralGoogle Scholar
  100. 100.
    Zhu S, Rezvani M, Harbell J, Mattis AN, Wolfe AR, Benet LZ, Willenbring H, Ding S (2014) Mouse liver repopulation with hepatocytes generated from human fibroblasts. Nature 508(7494):93–97.  https://doi.org/10.1038/nature13020 PubMedPubMedCentralGoogle Scholar
  101. 101.
    Efe JA, Hilcove S, Kim J, Zhou H, Ouyang K, Wang G, Chen J, Ding S (2011) Conversion of mouse fibroblasts into cardiomyocytes using a direct reprogramming strategy. Nat Cell Biol 13(3):215–222.  https://doi.org/10.1038/ncb2164 PubMedGoogle Scholar
  102. 102.
    Li J, Huang NF, Zou J, Laurent TJ, Lee JC, Okogbaa J, Cooke JP, Ding S (2013) Conversion of human fibroblasts to functional endothelial cells by defined factors. Arterioscler Thromb Vasc Biol 33(6):1366–1375.  https://doi.org/10.1161/ATVBAHA.112.301167 PubMedPubMedCentralGoogle Scholar
  103. 103.
    Szabo E, Rampalli S, Risueno RM, Schnerch A, Mitchell R, Fiebig-Comyn A, Levadoux-Martin M, Bhatia M (2010) Direct conversion of human fibroblasts to multilineage blood progenitors. Nature 468(7323):521–526.  https://doi.org/10.1038/nature09591 PubMedGoogle Scholar
  104. 104.
    Maza I, Caspi I, Zviran A, Chomsky E, Rais Y, Viukov S, Geula S, Buenrostro JD, Weinberger L, Krupalnik V, Hanna S, Zerbib M, Dutton JR, Greenleaf WJ, Massarwa R, Novershtern N, Hanna JH (2015) Transient acquisition of pluripotency during somatic cell transdifferentiation with iPSC reprogramming factors. Nat Biotechnol 33(7):769–774.  https://doi.org/10.1038/nbt.3270 PubMedPubMedCentralGoogle Scholar
  105. 105.
    Marro S, Pang ZP, Yang N, Tsai MC, Qu K, Chang HY, Sudhof TC, Wernig M (2011) Direct lineage conversion of terminally differentiated hepatocytes to functional neurons. Cell Stem Cell 9(4):374–382.  https://doi.org/10.1016/j.stem.2011.09.002 PubMedPubMedCentralGoogle Scholar
  106. 106.
    Qiang L, Fujita R, Yamashita T, Angulo S, Rhinn H, Rhee D, Doege C, Chau L, Aubry L, Vanti WB, Moreno H, Abeliovich A (2011) Directed conversion of Alzheimer’s disease patient skin fibroblasts into functional neurons. Cell 146(3):359–371.  https://doi.org/10.1016/j.cell.2011.07.007 PubMedPubMedCentralGoogle Scholar
  107. 107.
    Yoo AS, Sun AX, Li L, Shcheglovitov A, Portmann T, Li Y, Lee-Messer C, Dolmetsch RE, Tsien RW, Crabtree GR (2011) MicroRNA-mediated conversion of human fibroblasts to neurons. Nature 476(7359):228–231.  https://doi.org/10.1038/nature10323 PubMedPubMedCentralGoogle Scholar
  108. 108.
    Pfisterer U, Kirkeby A, Torper O, Wood J, Nelander J, Dufour A, Bjorklund A, Lindvall O, Jakobsson J, Parmar M (2011) Direct conversion of human fibroblasts to dopaminergic neurons. Proc Natl Acad Sci USA 108(25):10343–10348.  https://doi.org/10.1073/pnas.1105135108 PubMedPubMedCentralGoogle Scholar
  109. 109.
    Verrijzer CP, Alkema MJ, van Weperen WW, Van Leeuwen HC, Strating MJ, van der Vliet PC (1992) The DNA binding specificity of the bipartite POU domain and its subdomains. EMBO J 11(13):4993–5003PubMedPubMedCentralGoogle Scholar
  110. 110.
    Heinz S, Benner C, Spann N, Bertolino E, Lin YC, Laslo P, Cheng JX, Murre C, Singh H, Glass CK (2010) Simple combinations of lineage-determining transcription factors prime cis-regulatory elements required for macrophage and B cell identities. Mol Cell 38(4):576–589.  https://doi.org/10.1016/j.molcel.2010.05.004 PubMedPubMedCentralGoogle Scholar
  111. 111.
    Assa-Munt N, Mortishire-Smith RJ, Aurora R, Herr W, Wright PE (1993) The solution structure of the Oct-1 POU-specific domain reveals a striking similarity to the bacteriophage lambda repressor DNA-binding domain. Cell 73(1):193–205PubMedGoogle Scholar
  112. 112.
    Dekker N, Cox M, Boelens R, Verrijzer CP, van der Vliet PC, Kaptein R (1993) Solution structure of the POU-specific DNA-binding domain of Oct-1. Nature 362(6423):852–855.  https://doi.org/10.1038/362852a0 PubMedGoogle Scholar
  113. 113.
    Cox M, van Tilborg PJ, de Laat W, Boelens R, van Leeuwen HC, van der Vliet PC, Kaptein R (1995) Solution structure of the Oct-1 POU homeodomain determined by NMR and restrained molecular dynamics. J Biomol NMR 6(1):23–32PubMedGoogle Scholar
  114. 114.
    Morita EH, Shirakawa M, Hayashi F, Imagawa M, Kyogoku Y (1995) Structure of the Oct-3 POU-homeodomain in solution, as determined by triple resonance heteronuclear multidimensional NMR spectroscopy. Protein Sci 4(4):729–739.  https://doi.org/10.1002/pro.5560040412 PubMedPubMedCentralGoogle Scholar
  115. 115.
    Klemm JD, Rould MA, Aurora R, Herr W, Pabo CO (1994) Crystal structure of the Oct-1 POU domain bound to an octamer site: DNA recognition with tethered DNA-binding modules. Cell 77(1):21–32PubMedGoogle Scholar
  116. 116.
    Ferraris L, Stewart AP, Kang J, DeSimone AM, Gemberling M, Tantin D, Fairbrother WG (2011) Combinatorial binding of transcription factors in the pluripotency control regions of the genome. Genome Res 21(7):1055–1064.  https://doi.org/10.1101/gr.115824.110 PubMedPubMedCentralGoogle Scholar
  117. 117.
    Baburajendran N, Jauch R, Tan CY, Narasimhan K, Kolatkar PR (2011) Structural basis for the cooperative DNA recognition by Smad4 MH1 dimers. Nucleic Acids Res 39(18):8213–8222.  https://doi.org/10.1093/nar/gkr500 PubMedPubMedCentralGoogle Scholar
  118. 118.
    Kim S, Brostromer E, Xing D, Jin J, Chong S, Ge H, Wang S, Gu C, Yang L, Gao YQ, Su XD, Sun Y, Xie XS (2013) Probing allostery through DNA. Science 339(6121):816–819.  https://doi.org/10.1126/science.1229223 PubMedPubMedCentralGoogle Scholar
  119. 119.
    Narasimhan K, Pillay S, Huang YH, Jayabal S, Udayasuryan B, Veerapandian V, Kolatkar P, Cojocaru V, Pervushin K, Jauch R (2015) DNA-mediated cooperativity facilitates the co-selection of cryptic enhancer sequences by SOX2 and PAX6 transcription factors. Nucleic Acids Res 43(3):1513–1528.  https://doi.org/10.1093/nar/gku1390 PubMedPubMedCentralGoogle Scholar
  120. 120.
    Merino F, Bouvier B, Cojocaru V (2015) Cooperative DNA recognition modulated by an interplay between protein–protein interactions and DNA-mediated allostery. PLoS Comput Biol 11(6):e1004287.  https://doi.org/10.1371/journal.pcbi.1004287 PubMedPubMedCentralGoogle Scholar
  121. 121.
    Badis G, Berger MF, Philippakis AA, Talukder S, Gehrke AR, Jaeger SA, Chan ET, Metzler G, Vedenko A, Chen X, Kuznetsov H, Wang CF, Coburn D, Newburger DE, Morris Q, Hughes TR, Bulyk ML (2009) Diversity and complexity in DNA recognition by transcription factors. Science 324(5935):1720–1723.  https://doi.org/10.1126/science.1162327 PubMedPubMedCentralGoogle Scholar
  122. 122.
    Weirauch MT, Yang A, Albu M, Cote AG, Montenegro-Montero A, Drewe P, Najafabadi HS, Lambert SA, Mann I, Cook K, Zheng H, Goity A, van Bakel H, Lozano JC, Galli M, Lewsey MG, Huang E, Mukherjee T, Chen X, Reece-Hoyes JS, Govindarajan S, Shaulsky G, Walhout AJM, Bouget FY, Ratsch G, Larrondo LF, Ecker JR, Hughes TR (2014) Determination and inference of eukaryotic transcription factor sequence specificity. Cell 158(6):1431–1443.  https://doi.org/10.1016/j.cell.2014.08.009 PubMedPubMedCentralGoogle Scholar
  123. 123.
    Takayama Y, Clore GM (2011) Intra- and intermolecular translocation of the bi-domain transcription factor Oct1 characterized by liquid crystal and paramagnetic NMR. Proc Natl Acad Sci USA 108(22):E169–176.  https://doi.org/10.1073/pnas.1100050108 PubMedPubMedCentralGoogle Scholar
  124. 124.
    Kemler I, Schreiber E, Muller MM, Matthias P, Schaffner W (1989) Octamer transcription factors bind to two different sequence motifs of the immunoglobulin heavy chain promoter. EMBO J 8(7):2001–2008PubMedPubMedCentralGoogle Scholar
  125. 125.
    LeBowitz JH, Clerc RG, Brenowitz M, Sharp PA (1989) The Oct-2 protein binds cooperatively to adjacent octamer sites. Genes Dev 3(10):1625–1638PubMedGoogle Scholar
  126. 126.
    Poellinger L, Roeder RG (1989) Octamer transcription factors 1 and 2 each bind to two different functional elements in the immunoglobulin heavy-chain promoter. Mol Cell Biol 9(2):747–756PubMedPubMedCentralGoogle Scholar
  127. 127.
    Rhee JM, Gruber CA, Brodie TB, Trieu M, Turner EE (1998) Highly cooperative homodimerization is a conserved property of neural POU proteins. J Biol Chem 273(51):34196–34205PubMedGoogle Scholar
  128. 128.
    Jacobson EM, Li P, Leon-del-Rio A, Rosenfeld MG, Aggarwal AK (1997) Structure of Pit-1 POU domain bound to DNA as a dimer: unexpected arrangement and flexibility. Genes Dev 11(2):198–212PubMedGoogle Scholar
  129. 129.
    Tomilin A, Remenyi A, Lins K, Bak H, Leidel S, Vriend G, Wilmanns M, Scholer HR (2000) Synergism with the coactivator OBF-1 (OCA-B, BOB-1) is mediated by a specific POU dimer configuration. Cell 103(6):853–864PubMedGoogle Scholar
  130. 130.
    Remenyi A, Tomilin A, Pohl E, Lins K, Philippsen A, Reinbold R, Scholer HR, Wilmanns M (2001) Differential dimer activities of the transcription factor Oct-1 by DNA-induced interface swapping. Mol Cell 8(3):569–580PubMedGoogle Scholar
  131. 131.
    Jauch R, Choo SH, Ng CK, Kolatkar PR (2011) Crystal structure of the dimeric Oct6 (POU3f1) POU domain bound to palindromic MORE DNA. Proteins 79(2):674–677.  https://doi.org/10.1002/prot.22916 PubMedGoogle Scholar
  132. 132.
    Scully KM, Jacobson EM, Jepsen K, Lunyak V, Viadiu H, Carriere C, Rose DW, Hooshmand F, Aggarwal AK, Rosenfeld MG (2000) Allosteric effects of Pit-1 DNA sites on long-term repression in cell type specification. Science 290(5494):1127–1131PubMedGoogle Scholar
  133. 133.
    Botquin V, Hess H, Fuhrmann G, Anastassiadis C, Gross MK, Vriend G, Scholer HR (1998) New POU dimer configuration mediates antagonistic control of an osteopontin preimplantation enhancer by Oct-4 and Sox-2. Genes Dev 12(13):2073–2090PubMedPubMedCentralGoogle Scholar
  134. 134.
    Skowronska-Krawczyk D, Ma Q, Schwartz M, Scully K, Li W, Liu Z, Taylor H, Tollkuhn J, Ohgi KA, Notani D, Kohwi Y, Kohwi-Shigematsu T, Rosenfeld MG (2014) Required enhancer-matrin-3 network interactions for a homeodomain transcription program. Nature 514(7521):257–261.  https://doi.org/10.1038/nature13573 PubMedPubMedCentralGoogle Scholar
  135. 135.
    Mistri TK, Devasia AG, Chu LT, Ng WP, Halbritter F, Colby D, Martynoga B, Tomlinson SR, Chambers I, Robson P, Wohland T (2015) Selective influence of Sox2 on POU transcription factor binding in embryonic and neural stem cells. EMBO Rep 16(9):1177–1191.  https://doi.org/10.15252/embr.201540467 PubMedPubMedCentralGoogle Scholar
  136. 136.
    Sharov AA, Ko MS (2009) Exhaustive search for over-represented DNA sequence motifs with CisFinder. DNA Res 16(5):261–273.  https://doi.org/10.1093/dnares/dsp014 PubMedPubMedCentralGoogle Scholar
  137. 137.
    Lins K, Remenyi A, Tomilin A, Massa S, Wilmanns M, Matthias P, Scholer HR (2003) OBF1 enhances transcriptional potential of Oct1. EMBO J 22(9):2188–2198.  https://doi.org/10.1093/emboj/cdg199 PubMedPubMedCentralGoogle Scholar
  138. 138.
    BabuRajendran N, Palasingam P, Narasimhan K, Sun W, Prabhakar S, Jauch R, Kolatkar PR (2010) Structure of Smad1 MH1/DNA complex reveals distinctive rearrangements of BMP and TGF-beta effectors. Nucleic Acids Res 38(10):3477–3488.  https://doi.org/10.1093/nar/gkq046 PubMedPubMedCentralGoogle Scholar
  139. 139.
    Jolma A, Yan J, Whitington T, Toivonen J, Nitta KR, Rastas P, Morgunova E, Enge M, Taipale M, Wei G, Palin K, Vaquerizas JM, Vincentelli R, Luscombe NM, Hughes TR, Lemaire P, Ukkonen E, Kivioja T, Taipale J (2013) DNA-binding specificities of human transcription factors. Cell 152(1–2):327–339.  https://doi.org/10.1016/j.cell.2012.12.009 PubMedGoogle Scholar
  140. 140.
    Yin Y, Morgunova E, Jolma A, Kaasinen E, Sahu B, Khund-Sayeed S, Das PK, Kivioja T, Dave K, Zhong F, Nitta KR, Taipale M, Popov A, Ginno PA, Domcke S, Yan J, Schubeler D, Vinson C, Taipale J (2017) Impact of cytosine methylation on DNA binding specificities of human transcription factors. Science 356(6337):eaaj2239.  https://doi.org/10.1126/science.aaj2239 PubMedGoogle Scholar
  141. 141.
    Palasingam P, Jauch R, Ng CK, Kolatkar PR (2009) The structure of Sox17 bound to DNA reveals a conserved bending topology but selective protein interaction platforms. J Mol Biol 388(3):619–630.  https://doi.org/10.1016/j.jmb.2009.03.055 PubMedGoogle Scholar
  142. 142.
    Remenyi A, Lins K, Nissen LJ, Reinbold R, Scholer HR, Wilmanns M (2003) Crystal structure of a POU/HMG/DNA ternary complex suggests differential assembly of Oct4 and Sox2 on two enhancers. Genes Dev 17(16):2048–2059.  https://doi.org/10.1101/gad.269303 PubMedPubMedCentralGoogle Scholar
  143. 143.
    Jauch R, Ng CK, Narasimhan K, Kolatkar PR (2012) Crystal structure of the Sox4 HMG/DNA complex suggests a mechanism for the positional interdependence in DNA recognition. Biochem J 443(1):39–47.  https://doi.org/10.1042/BJ20111768 PubMedGoogle Scholar
  144. 144.
    Klaus M, Prokoph N, Girbig M, Wang X, Huang YH, Srivastava Y, Hou L, Narasimhan K, Kolatkar PR, Francois M, Jauch R (2016) Structure and decoy-mediated inhibition of the SOX18/Prox1–DNA interaction. Nucleic Acids Res 44(8):3922–3935.  https://doi.org/10.1093/nar/gkw130 PubMedPubMedCentralGoogle Scholar
  145. 145.
    Werner MH, Huth JR, Gronenborn AM, Clore GM (1995) Molecular basis of human 46X, Y sex reversal revealed from the three-dimensional solution structure of the human SRY-DNA complex. Cell 81(5):705–714PubMedGoogle Scholar
  146. 146.
    Hou L, Srivastava Y, Jauch R (2016) Molecular basis for the genome engagement by Sox proteins. Semin Cell Dev Biol.  https://doi.org/10.1016/j.semcdb.2016.08.005 PubMedCentralGoogle Scholar
  147. 147.
    Ambrosetti DC, Basilico C, Dailey L (1997) Synergistic activation of the fibroblast growth factor 4 enhancer by Sox2 and Oct-3 depends on protein–protein interactions facilitated by a specific spatial arrangement of factor binding sites. Mol Cell Biol 17(11):6321–6329PubMedPubMedCentralGoogle Scholar
  148. 148.
    Dailey L, Yuan H, Basilico C (1994) Interaction between a novel F9-specific factor and octamer-binding proteins is required for cell-type-restricted activity of the fibroblast growth factor 4 enhancer. Mol Cell Biol 14(12):7758–7769PubMedPubMedCentralGoogle Scholar
  149. 149.
    Nishimoto M, Fukushima A, Okuda A, Muramatsu M (1999) The gene for the embryonic stem cell coactivator UTF1 carries a regulatory element which selectively interacts with a complex composed of Oct-3/4 and Sox-2. Mol Cell Biol 19(8):5453–5465PubMedPubMedCentralGoogle Scholar
  150. 150.
    Nakatake Y, Fukui N, Iwamatsu Y, Masui S, Takahashi K, Yagi R, Yagi K, Miyazaki J, Matoba R, Ko MS, Niwa H (2006) Klf4 cooperates with Oct3/4 and Sox2 to activate the Lefty1 core promoter in embryonic stem cells. Mol Cell Biol 26(20):7772–7782.  https://doi.org/10.1128/MCB.00468-06 PubMedPubMedCentralGoogle Scholar
  151. 151.
    Tokuzawa Y, Kaiho E, Maruyama M, Takahashi K, Mitsui K, Maeda M, Niwa H, Yamanaka S (2003) Fbx15 is a novel target of Oct3/4 but is dispensable for embryonic stem cell self-renewal and mouse development. Mol Cell Biol 23(8):2699–2708PubMedPubMedCentralGoogle Scholar
  152. 152.
    Rodda DJ, Chew JL, Lim LH, Loh YH, Wang B, Ng HH, Robson P (2005) Transcriptional regulation of nanog by OCT4 and SOX2. J Biol Chem 280(26):24731–24737.  https://doi.org/10.1074/jbc.M502573200 PubMedGoogle Scholar
  153. 153.
    Kuroda T, Tada M, Kubota H, Kimura H, Hatano SY, Suemori H, Nakatsuji N, Tada T (2005) Octamer and Sox elements are required for transcriptional cis regulation of Nanog gene expression. Mol Cell Biol 25(6):2475–2485.  https://doi.org/10.1128/MCB.25.6.2475-2485.2005 PubMedPubMedCentralGoogle Scholar
  154. 154.
    Tomioka M, Nishimoto M, Miyagi S, Katayanagi T, Fukui N, Niwa H, Muramatsu M, Okuda A (2002) Identification of Sox-2 regulatory region which is under the control of Oct-3/4-Sox-2 complex. Nucleic Acids Res 30(14):3202–3213PubMedPubMedCentralGoogle Scholar
  155. 155.
    Chew JL, Loh YH, Zhang W, Chen X, Tam WL, Yeap LS, Li P, Ang YS, Lim B, Robson P, Ng HH (2005) Reciprocal transcriptional regulation of Pou5f1 and Sox2 via the Oct4/Sox2 complex in embryonic stem cells. Mol Cell Biol 25(14):6031–6046.  https://doi.org/10.1128/MCB.25.14.6031-6046.2005 PubMedPubMedCentralGoogle Scholar
  156. 156.
    Okumura-Nakanishi S, Saito M, Niwa H, Ishikawa F (2005) Oct-3/4 and Sox2 regulate Oct-3/4 gene in embryonic stem cells. J Biol Chem 280(7):5307–5317.  https://doi.org/10.1074/jbc.M410015200 PubMedGoogle Scholar
  157. 157.
    Boyer LA, Lee TI, Cole MF, Johnstone SE, Levine SS, Zucker JP, Guenther MG, Kumar RM, Murray HL, Jenner RG, Gifford DK, Melton DA, Jaenisch R, Young RA (2005) Core transcriptional regulatory circuitry in human embryonic stem cells. Cell 122(6):947–956.  https://doi.org/10.1016/j.cell.2005.08.020 PubMedPubMedCentralGoogle Scholar
  158. 158.
    Loh YH, Wu Q, Chew JL, Vega VB, Zhang W, Chen X, Bourque G, George J, Leong B, Liu J, Wong KY, Sung KW, Lee CW, Zhao XD, Chiu KP, Lipovich L, Kuznetsov VA, Robson P, Stanton LW, Wei CL, Ruan Y, Lim B, Ng HH (2006) The Oct4 and Nanog transcription network regulates pluripotency in mouse embryonic stem cells. Nat Genet 38(4):431–440.  https://doi.org/10.1038/ng1760 PubMedGoogle Scholar
  159. 159.
    Chen X, Xu H, Yuan P, Fang F, Huss M, Vega VB, Wong E, Orlov YL, Zhang W, Jiang J, Loh YH, Yeo HC, Yeo ZX, Narang V, Govindarajan KR, Leong B, Shahab A, Ruan Y, Bourque G, Sung WK, Clarke ND, Wei CL, Ng HH (2008) Integration of external signaling pathways with the core transcriptional network in embryonic stem cells. Cell 133(6):1106–1117.  https://doi.org/10.1016/j.cell.2008.04.043 PubMedGoogle Scholar
  160. 160.
    Kunarso G, Chia NY, Jeyakani J, Hwang C, Lu X, Chan YS, Ng HH, Bourque G (2010) Transposable elements have rewired the core regulatory network of human embryonic stem cells. Nat Genet 42(7):631–634.  https://doi.org/10.1038/ng.600 PubMedGoogle Scholar
  161. 161.
    Jauch R, Aksoy I, Hutchins AP, Ng CK, Tian XF, Chen J, Palasingam P, Robson P, Stanton LW, Kolatkar PR (2011) Conversion of Sox17 into a pluripotency reprogramming factor by reengineering its association with Oct4 on DNA. Stem Cells 29(6):940–951.  https://doi.org/10.1002/stem.639 PubMedGoogle Scholar
  162. 162.
    Tapia N, MacCarthy C, Esch D, Gabriele Marthaler A, Tiemann U, Arauzo-Bravo MJ, Jauch R, Cojocaru V, Scholer HR (2015) Dissecting the role of distinct OCT4-SOX2 heterodimer configurations in pluripotency. Sci Rep 5:13533.  https://doi.org/10.1038/srep13533 PubMedPubMedCentralGoogle Scholar
  163. 163.
    Chen J, Chen X, Li M, Liu X, Gao Y, Kou X, Zhao Y, Zheng W, Zhang X, Huo Y, Chen C, Wu Y, Wang H, Jiang C, Gao S (2016) Hierarchical Oct4 binding in concert with primed epigenetic rearrangements during somatic cell reprogramming. Cell Rep 14(6):1540–1554.  https://doi.org/10.1016/j.celrep.2016.01.013 PubMedGoogle Scholar
  164. 164.
    Chronis C, Fiziev P, Papp B, Butz S, Bonora G, Sabri S, Ernst J, Plath K (2017) Cooperative binding of transcription factors orchestrates reprogramming. Cell 168(3):442–459 e420.  https://doi.org/10.1016/j.cell.2016.12.016 PubMedPubMedCentralGoogle Scholar
  165. 165.
    Chen J, Zhang Z, Li L, Chen BC, Revyakin A, Hajj B, Legant W, Dahan M, Lionnet T, Betzig E, Tjian R, Liu Z (2014) Single-molecule dynamics of enhanceosome assembly in embryonic stem cells. Cell 156(6):1274–1285.  https://doi.org/10.1016/j.cell.2014.01.062 PubMedPubMedCentralGoogle Scholar
  166. 166.
    Jolma A, Yin Y, Nitta KR, Dave K, Popov A, Taipale M, Enge M, Kivioja T, Morgunova E, Taipale J (2015) DNA-dependent formation of transcription factor pairs alters their binding specificity. Nature 527(7578):384–388.  https://doi.org/10.1038/nature15518 PubMedGoogle Scholar
  167. 167.
    Dailey L, Basilico C (2001) Coevolution of HMG domains and homeodomains and the generation of transcriptional regulation by Sox/POU complexes. J Cell Physiol 186(3):315–328PubMedGoogle Scholar
  168. 168.
    Kamachi Y, Uchikawa M, Kondoh H (2000) Pairing SOX off: with partners in the regulation of embryonic development. Trends Genet 16(4):182–187PubMedGoogle Scholar
  169. 169.
    Wilson M, Koopman P (2002) Matching SOX: partner proteins and co-factors of the SOX family of transcriptional regulators. Curr Opin Genet Dev 12(4):441–446PubMedGoogle Scholar
  170. 170.
    Kuhlbrodt K, Herbarth B, Sock E, Enderich J, Hermans-Borgmeyer I, Wegner M (1998) Cooperative function of POU proteins and SOX proteins in glial cells. J Biol Chem 273(26):16050–16057PubMedGoogle Scholar
  171. 171.
    Kuhlbrodt K, Herbarth B, Sock E, Hermans-Borgmeyer I, Wegner M (1998) Sox10, a novel transcriptional modulator in glial cells. J Neurosci 18(1):237–250PubMedGoogle Scholar
  172. 172.
    Tanaka S, Kamachi Y, Tanouchi A, Hamada H, Jing N, Kondoh H (2004) Interplay of SOX and POU factors in regulation of the Nestin gene in neural primordial cells. Mol Cell Biol 24(20):8834–8846.  https://doi.org/10.1128/MCB.24.20.8834-8846.2004 PubMedPubMedCentralGoogle Scholar
  173. 173.
    Catena R, Tiveron C, Ronchi A, Porta S, Ferri A, Tatangelo L, Cavallaro M, Favaro R, Ottolenghi S, Reinbold R, Scholer H, Nicolis SK (2004) Conserved POU binding DNA sites in the Sox2 upstream enhancer regulate gene expression in embryonic and neural stem cells. J Biol Chem 279(40):41846–41857.  https://doi.org/10.1074/jbc.M405514200 PubMedGoogle Scholar
  174. 174.
    Lodato MA, Ng CW, Wamstad JA, Cheng AW, Thai KK, Fraenkel E, Jaenisch R, Boyer LA (2013) SOX2 co-occupies distal enhancer elements with distinct POU factors in ESCs and NPCs to specify cell state. PLoS Genet 9(2):e1003288.  https://doi.org/10.1371/journal.pgen.1003288 PubMedPubMedCentralGoogle Scholar
  175. 175.
    Chang YK, Srivastava Y, Hu C, Joyce A, Yang X, Zuo Z, Havranek JJ, Stormo GD, Jauch R (2017) Quantitative profiling of selective Sox/POU pairing on hundreds of sequences in parallel by Coop-seq. Nucleic Acids Res 45(2):832–845.  https://doi.org/10.1093/nar/gkw1198 PubMedGoogle Scholar
  176. 176.
    Nishimoto M, Miyagi S, Yamagishi T, Sakaguchi T, Niwa H, Muramatsu M, Okuda A (2005) Oct-3/4 maintains the proliferative embryonic stem cell state via specific binding to a variant octamer sequence in the regulatory region of the UTF1 locus. Mol Cell Biol 25(12):5084–5094.  https://doi.org/10.1128/MCB.25.12.5084-5094.2005 PubMedPubMedCentralGoogle Scholar
  177. 177.
    Ng CK, Li NX, Chee S, Prabhakar S, Kolatkar PR, Jauch R (2012) Deciphering the Sox–Oct partner code by quantitative cooperativity measurements. Nucleic Acids Res 40(11):4933–4941.  https://doi.org/10.1093/nar/gks153 PubMedPubMedCentralGoogle Scholar
  178. 178.
    Aksoy I, Jauch R, Chen J, Dyla M, Divakar U, Bogu GK, Teo R, Leng Ng CK, Herath W, Lili S, Hutchins AP, Robson P, Kolatkar PR, Stanton LW (2013) Oct4 switches partnering from Sox2 to Sox17 to reinterpret the enhancer code and specify endoderm. EMBO J 32(7):938–953.  https://doi.org/10.1038/emboj.2013.31 PubMedPubMedCentralGoogle Scholar
  179. 179.
    Merino F, Ng CK, Veerapandian V, Scholer HR, Jauch R, Cojocaru V (2014) Structural basis for the SOX-dependent genomic redistribution of OCT4 in stem cell differentiation. Structure 22(9):1274–1286.  https://doi.org/10.1016/j.str.2014.06.014 PubMedGoogle Scholar
  180. 180.
    Aksoy I, Jauch R, Eras V, Chng WB, Chen J, Divakar U, Ng CK, Kolatkar PR, Stanton LW (2013) Sox transcription factors require selective interactions with Oct4 and specific transactivation functions to mediate reprogramming. Stem Cells 31(12):2632–2646.  https://doi.org/10.1002/stem.1522 PubMedGoogle Scholar
  181. 181.
    Niwa H, Nakamura A, Urata M, Shirae-Kurabayashi M, Kuraku S, Russell S, Ohtsuka S (2016) The evolutionally-conserved function of group B1 Sox family members confers the unique role of Sox2 in mouse ES cells. BMC Evol Biol 16:173.  https://doi.org/10.1186/s12862-016-0755-4 PubMedPubMedCentralGoogle Scholar
  182. 182.
    Irie N, Weinberger L, Tang WW, Kobayashi T, Viukov S, Manor YS, Dietmann S, Hanna JH, Surani MA (2015) SOX17 is a critical specifier of human primordial germ cell fate. Cell 160(1–2):253–268.  https://doi.org/10.1016/j.cell.2014.12.013 PubMedPubMedCentralGoogle Scholar
  183. 183.
    Knaupp AS, Buckberry S, Pflueger J, Lim SM, Ford E, Larcombe MR, Rossello FJ, de Mendoza A, Alaei S, Firas J, Holmes ML, Nair SS, Clark SJ, Nefzger CM, Lister R, Polo JM (2017) Transient and permanent reconfiguration of chromatin and transcription factor occupancy drive reprogramming. Cell Stem Cell 21(6):834–845 e836.  https://doi.org/10.1016/j.stem.2017.11.007 PubMedGoogle Scholar
  184. 184.
    Williams DC Jr, Cai M, Clore GM (2004) Molecular basis for synergistic transcriptional activation by Oct1 and Sox2 revealed from the solution structure of the 42-kDa Oct1.Sox2.Hoxb1-DNA ternary transcription factor complex. J Biol Chem 279(2):1449–1457.  https://doi.org/10.1074/jbc.M309790200 PubMedGoogle Scholar
  185. 185.
    Pereira JH, Kim SH (2009) Structure of human Brn-5 transcription factor in complex with CRH gene promoter. J Struct Biol 167(2):159–165.  https://doi.org/10.1016/j.jsb.2009.05.003 PubMedGoogle Scholar
  186. 186.
    Esch D, Vahokoski J, Groves MR, Pogenberg V, Cojocaru V, Vom Bruch H, Han D, Drexler HC, Arauzo-Bravo MJ, Ng CK, Jauch R, Wilmanns M, Scholer HR (2013) A unique Oct4 interface is crucial for reprogramming to pluripotency. Nat Cell Biol 15(3):295–301.  https://doi.org/10.1038/ncb2680 PubMedGoogle Scholar
  187. 187.
    Jin W, Wang L, Zhu F, Tan W, Lin W, Chen D, Sun Q, Xia Z (2016) Critical POU domain residues confer Oct4 uniqueness in somatic cell reprogramming. Sci Rep 6:20818.  https://doi.org/10.1038/srep20818 PubMedPubMedCentralGoogle Scholar
  188. 188.
    Kong X, Liu J, Li L, Yue L, Zhang L, Jiang H, Xie X, Luo C (2015) Functional interplay between the RK motif and linker segment dictates Oct4-DNA recognition. Nucleic Acids Res 43(9):4381–4392.  https://doi.org/10.1093/nar/gkv323 PubMedPubMedCentralGoogle Scholar
  189. 189.
    Zaret KS, Mango SE (2016) Pioneer transcription factors, chromatin dynamics, and cell fate control. Curr Opin Genet Dev 37:76–81.  https://doi.org/10.1016/j.gde.2015.12.003 PubMedPubMedCentralGoogle Scholar
  190. 190.
    Gualdi R, Bossard P, Zheng M, Hamada Y, Coleman JR, Zaret KS (1996) Hepatic specification of the gut endoderm in vitro: cell signaling and transcriptional control. Genes Dev 10(13):1670–1682PubMedGoogle Scholar
  191. 191.
    Caravaca JM, Donahue G, Becker JS, He X, Vinson C, Zaret KS (2013) Bookmarking by specific and nonspecific binding of FoxA1 pioneer factor to mitotic chromosomes. Genes Dev 27(3):251–260.  https://doi.org/10.1101/gad.206458.112 PubMedPubMedCentralGoogle Scholar
  192. 192.
    Clark KL, Halay ED, Lai E, Burley SK (1993) Co-crystal structure of the HNF-3/fork head DNA-recognition motif resembles histone H5. Nature 364(6436):412–420.  https://doi.org/10.1038/364412a0 PubMedGoogle Scholar
  193. 193.
    Ramakrishnan V, Finch JT, Graziano V, Lee PL, Sweet RM (1993) Crystal structure of globular domain of histone H5 and its implications for nucleosome binding. Nature 362(6417):219–223.  https://doi.org/10.1038/362219a0 PubMedGoogle Scholar
  194. 194.
    Cirillo LA, McPherson CE, Bossard P, Stevens K, Cherian S, Shim EY, Clark KL, Burley SK, Zaret KS (1998) Binding of the winged-helix transcription factor HNF3 to a linker histone site on the nucleosome. EMBO J 17(1):244–254.  https://doi.org/10.1093/emboj/17.1.244 PubMedPubMedCentralGoogle Scholar
  195. 195.
    Bednar J, Garcia-Saez I, Boopathi R, Cutter AR, Papai G, Reymer A, Syed SH, Lone IN, Tonchev O, Crucifix C, Menoni H, Papin C, Skoufias DA, Kurumizaka H, Lavery R, Hamiche A, Hayes JJ, Schultz P, Angelov D, Petosa C, Dimitrov S (2017) Structure and dynamics of a 197 bp nucleosome in complex with linker histone H1. Mol Cell 66(3):384–397 e388.  https://doi.org/10.1016/j.molcel.2017.04.012 PubMedGoogle Scholar
  196. 196.
    Song F, Chen P, Sun D, Wang M, Dong L, Liang D, Xu RM, Zhu P, Li G (2014) Cryo-EM study of the chromatin fiber reveals a double helix twisted by tetranucleosomal units. Science 344(6182):376–380.  https://doi.org/10.1126/science.1251413 PubMedGoogle Scholar
  197. 197.
    Cirillo LA, Lin FR, Cuesta I, Friedman D, Jarnik M, Zaret KS (2002) Opening of compacted chromatin by early developmental transcription factors HNF3 (FoxA) and GATA-4. Mol Cell 9(2):279–289PubMedGoogle Scholar
  198. 198.
    Soufi A, Donahue G, Zaret KS (2012) Facilitators and impediments of the pluripotency reprogramming factors’ initial engagement with the genome. Cell 151(5):994–1004.  https://doi.org/10.1016/j.cell.2012.09.045 PubMedPubMedCentralGoogle Scholar
  199. 199.
    Soufi A, Garcia MF, Jaroszewicz A, Osman N, Pellegrini M, Zaret KS (2015) Pioneer transcription factors target partial DNA motifs on nucleosomes to initiate reprogramming. Cell 161(3):555–568.  https://doi.org/10.1016/j.cell.2015.03.017 PubMedPubMedCentralGoogle Scholar
  200. 200.
    Zviran A, Mor N, Rais Y, Gingold H, Peles S, Chomsky E, Viukov S, Buenrostro JD, Weinberger L, Manor YS, Krupalnik V, Zerbib M, Hezroni H, Jaitin DA, Larastiaso D, Gilad S, Benjamin S, Mousa A, Ayyash M, Sheban D, Bayerl J, Castrejon AA, Massarwa R, Maza I, Hanna S, Amit I, Stelzer Y, Ulitsky I, Greenleaf WJ, Pilpel Y, Novershtern N, Hanna JH (2017) High-resolution dissection of conducive reprogramming trajectory to ground state pluripotency. bioRxiv.  https://doi.org/10.1101/184135 Google Scholar
  201. 201.
    Li D, Liu J, Yang X, Zhou C, Guo J, Wu C, Qin Y, Guo L, He J, Yu S, Liu H, Wang X, Wu F, Kuang J, Hutchins AP, Chen J, Pei D (2017) Chromatin accessibility dynamics during iPSC reprogramming. Cell Stem Cell 21(6):819–833 e816.  https://doi.org/10.1016/j.stem.2017.10.012 PubMedGoogle Scholar
  202. 202.
    Swinstead EE, Paakinaho V, Presman DM, Hager GL (2016) Pioneer factors and ATP-dependent chromatin remodeling factors interact dynamically: a new perspective: Multiple transcription factors can effect chromatin pioneer functions through dynamic interactions with ATP-dependent chromatin remodeling factors. BioEssays 38(11):1150–1157.  https://doi.org/10.1002/bies.201600137 PubMedGoogle Scholar
  203. 203.
    Zaret KS, Lerner J, Iwafuchi-Doi M (2016) Chromatin scanning by dynamic binding of pioneer factors. Mol Cell 62(5):665–667.  https://doi.org/10.1016/j.molcel.2016.05.024 PubMedPubMedCentralGoogle Scholar
  204. 204.
    Panne D, Maniatis T, Harrison SC (2007) An atomic model of the interferon-beta enhanceosome. Cell 129(6):1111–1123.  https://doi.org/10.1016/j.cell.2007.05.019 PubMedPubMedCentralGoogle Scholar
  205. 205.
    Kagey MH, Newman JJ, Bilodeau S, Zhan Y, Orlando DA, van Berkum NL, Ebmeier CC, Goossens J, Rahl PB, Levine SS, Taatjes DJ, Dekker J, Young RA (2010) Mediator and cohesin connect gene expression and chromatin architecture. Nature 467(7314):430–435.  https://doi.org/10.1038/nature09380 PubMedPubMedCentralGoogle Scholar
  206. 206.
    Nozawa K, Schneider TR, Cramer P (2017) Core mediator structure at 3.4 A extends model of transcription initiation complex. Nature 545(7653):248–251.  https://doi.org/10.1038/nature22328 PubMedGoogle Scholar
  207. 207.
    Azuara V, Perry P, Sauer S, Spivakov M, Jorgensen HF, John RM, Gouti M, Casanova M, Warnes G, Merkenschlager M, Fisher AG (2006) Chromatin signatures of pluripotent cell lines. Nat Cell Biol 8(5):532–538.  https://doi.org/10.1038/ncb1403 PubMedGoogle Scholar
  208. 208.
    Bernstein BE, Mikkelsen TS, Xie X, Kamal M, Huebert DJ, Cuff J, Fry B, Meissner A, Wernig M, Plath K, Jaenisch R, Wagschal A, Feil R, Schreiber SL, Lander ES (2006) A bivalent chromatin structure marks key developmental genes in embryonic stem cells. Cell 125(2):315–326.  https://doi.org/10.1016/j.cell.2006.02.041 PubMedGoogle Scholar
  209. 209.
    Mikkelsen TS, Ku M, Jaffe DB, Issac B, Lieberman E, Giannoukos G, Alvarez P, Brockman W, Kim TK, Koche RP, Lee W, Mendenhall E, O’Donovan A, Presser A, Russ C, Xie X, Meissner A, Wernig M, Jaenisch R, Nusbaum C, Lander ES, Bernstein BE (2007) Genome-wide maps of chromatin state in pluripotent and lineage-committed cells. Nature 448(7153):553–560.  https://doi.org/10.1038/nature06008 PubMedPubMedCentralGoogle Scholar
  210. 210.
    Koche RP, Smith ZD, Adli M, Gu H, Ku M, Gnirke A, Bernstein BE, Meissner A (2011) Reprogramming factor expression initiates widespread targeted chromatin remodeling. Cell Stem Cell 8(1):96–105.  https://doi.org/10.1016/j.stem.2010.12.001 PubMedPubMedCentralGoogle Scholar
  211. 211.
    Ang YS, Tsai SY, Lee DF, Monk J, Su J, Ratnakumar K, Ding J, Ge Y, Darr H, Chang B, Wang J, Rendl M, Bernstein E, Schaniel C, Lemischka IR (2011) Wdr5 mediates self-renewal and reprogramming via the embryonic stem cell core transcriptional network. Cell 145(2):183–197.  https://doi.org/10.1016/j.cell.2011.03.003 PubMedPubMedCentralGoogle Scholar
  212. 212.
    Mansour AA, Gafni O, Weinberger L, Zviran A, Ayyash M, Rais Y, Krupalnik V, Zerbib M, Amann-Zalcenstein D, Maza I, Geula S, Viukov S, Holtzman L, Pribluda A, Canaani E, Horn-Saban S, Amit I, Novershtern N, Hanna JH (2012) The H3K27 demethylase Utx regulates somatic and germ cell epigenetic reprogramming. Nature 488(7411):409–413.  https://doi.org/10.1038/nature11272 PubMedGoogle Scholar
  213. 213.
    Brumbaugh J, Hou Z, Russell JD, Howden SE, Yu P, Ledvina AR, Coon JJ, Thomson JA (2012) Phosphorylation regulates human OCT4. Proc Natl Acad Sci USA 109(19):7162–7168.  https://doi.org/10.1073/pnas.1203874109 PubMedPubMedCentralGoogle Scholar
  214. 214.
    Kang J, Gemberling M, Nakamura M, Whitby FG, Handa H, Fairbrother WG, Tantin D (2009) A general mechanism for transcription regulation by Oct1 and Oct4 in response to genotoxic and oxidative stress. Genes Dev 23(2):208–222.  https://doi.org/10.1101/gad.1750709 PubMedPubMedCentralGoogle Scholar
  215. 215.
    Lin Y, Yang Y, Li W, Chen Q, Li J, Pan X, Zhou L, Liu C, Chen C, He J, Cao H, Yao H, Zheng L, Xu X, Xia Z, Ren J, Xiao L, Li L, Shen B, Zhou H, Wang YJ (2012) Reciprocal regulation of Akt and Oct4 promotes the self-renewal and survival of embryonal carcinoma cells. Mol Cell 48(4):627–640.  https://doi.org/10.1016/j.molcel.2012.08.030 PubMedPubMedCentralGoogle Scholar
  216. 216.
    Nieto L, Joseph G, Stella A, Henri P, Burlet-Schiltz O, Monsarrat B, Clottes E, Erard M (2007) Differential effects of phosphorylation on DNA binding properties of N Oct-3 are dictated by protein/DNA complex structures. J Mol Biol 370(4):687–700.  https://doi.org/10.1016/j.jmb.2007.04.072 PubMedGoogle Scholar
  217. 217.
    Schild-Poulter C, Shih A, Tantin D, Yarymowich NC, Soubeyrand S, Sharp PA, Hache RJ (2007) DNA-PK phosphorylation sites on Oct-1 promote cell survival following DNA damage. Oncogene 26(27):3980–3988.  https://doi.org/10.1038/sj.onc.1210165 PubMedGoogle Scholar
  218. 218.
    Segil N, Roberts SB, Heintz N (1991) Mitotic phosphorylation of the Oct-1 homeodomain and regulation of Oct-1 DNA binding activity. Science 254(5039):1814–1816PubMedGoogle Scholar
  219. 219.
    Jang H, Kim TW, Yoon S, Choi SY, Kang TW, Kim SY, Kwon YW, Cho EJ, Youn HD (2012) O-GlcNAc regulates pluripotency and reprogramming by directly acting on core components of the pluripotency network. Cell Stem Cell 11(1):62–74.  https://doi.org/10.1016/j.stem.2012.03.001 PubMedGoogle Scholar
  220. 220.
    Kang J, Shen Z, Lim JM, Handa H, Wells L, Tantin D (2013) Regulation of Oct1/Pou2f1 transcription activity by O-GlcNAcylation. FASEB J 27(7):2807–2817.  https://doi.org/10.1096/fj.12-220897 PubMedPubMedCentralGoogle Scholar
  221. 221.
    Webster DM, Teo CF, Sun Y, Wloga D, Gay S, Klonowski KD, Wells L, Dougan ST (2009) O-GlcNAc modifications regulate cell survival and epiboly during zebrafish development. BMC Dev Biol 9:28.  https://doi.org/10.1186/1471-213X-9-28 PubMedPubMedCentralGoogle Scholar
  222. 222.
    Wei F, Scholer HR, Atchison ML (2007) Sumoylation of Oct4 enhances its stability, DNA binding, and transactivation. J Biol Chem 282(29):21551–21560.  https://doi.org/10.1074/jbc.M611041200 PubMedGoogle Scholar
  223. 223.
    Zhang Z, Liao B, Xu M, Jin Y (2007) Post-translational modification of POU domain transcription factor Oct-4 by SUMO-1. FASEB J 21(12):3042–3051.  https://doi.org/10.1096/fj.06-6914com PubMedGoogle Scholar
  224. 224.
    Kang J, Goodman B, Zheng Y, Tantin D (2011) Dynamic regulation of Oct1 during mitosis by phosphorylation and ubiquitination. PLoS One 6(8):e23872.  https://doi.org/10.1371/journal.pone.0023872 PubMedPubMedCentralGoogle Scholar
  225. 225.
    Xu HM, Liao B, Zhang QJ, Wang BB, Li H, Zhong XM, Sheng HZ, Zhao YX, Zhao YM, Jin Y (2004) Wwp2, an E3 ubiquitin ligase that targets transcription factor Oct-4 for ubiquitination. J Biol Chem 279(22):23495–23503.  https://doi.org/10.1074/jbc.M400516200 PubMedGoogle Scholar
  226. 226.
    Saxe JP, Tomilin A, Scholer HR, Plath K, Huang J (2009) Post-translational regulation of Oct4 transcriptional activity. PLoS One 4(2):e4467.  https://doi.org/10.1371/journal.pone.0004467 PubMedPubMedCentralGoogle Scholar
  227. 227.
    Lai JS, Cleary MA, Herr W (1992) A single amino acid exchange transfers VP16-induced positive control from the Oct-1 to the Oct-2 homeo domain. Genes Dev 6(11):2058–2065PubMedGoogle Scholar
  228. 228.
    Pomerantz JL, Kristie TM, Sharp PA (1992) Recognition of the surface of a homeo domain protein. Genes Dev 6(11):2047–2057PubMedGoogle Scholar
  229. 229.
    Dawson SJ, Palmer RD, Morris PJ, Latchman DS (1998) Functional role of position 22 in the homeodomain of Brn-3 transcription factors. NeuroReport 9(10):2305–2309PubMedGoogle Scholar
  230. 230.
    Fowler DM, Fields S (2014) Deep mutational scanning: a new style of protein science. Nat Methods 11(8):801–807.  https://doi.org/10.1038/nmeth.3027 PubMedPubMedCentralGoogle Scholar
  231. 231.
    Ding J, Xu H, Faiola F, Ma’ayan A, Wang J (2012) Oct4 links multiple epigenetic pathways to the pluripotency network. Cell Res 22(1):155–167.  https://doi.org/10.1038/cr.2011.179 PubMedGoogle Scholar
  232. 232.
    Pardo M, Lang B, Yu L, Prosser H, Bradley A, Babu MM, Choudhary J (2010) An expanded Oct4 interaction network: implications for stem cell biology, development, and disease. Cell Stem Cell 6(4):382–395.  https://doi.org/10.1016/j.stem.2010.03.004 PubMedPubMedCentralGoogle Scholar
  233. 233.
    van den Berg DL, Snoek T, Mullin NP, Yates A, Bezstarosti K, Demmers J, Chambers I, Poot RA (2010) An Oct4-centered protein interaction network in embryonic stem cells. Cell Stem Cell 6(4):369–381.  https://doi.org/10.1016/j.stem.2010.02.014 PubMedPubMedCentralGoogle Scholar
  234. 234.
    Arnold CD, Gerlach D, Stelzer C, Boryn LM, Rath M, Stark A (2013) Genome-wide quantitative enhancer activity maps identified by STARR-seq. Science 339(6123):1074–1077.  https://doi.org/10.1126/science.1232542 PubMedGoogle Scholar
  235. 235.
    Farnung L, Vos SM, Wigge C, Cramer P (2017) Nucleosome-Chd1 structure and implications for chromatin remodelling. Nature 550(7677):539–542.  https://doi.org/10.1038/nature24046 PubMedPubMedCentralGoogle Scholar
  236. 236.
    Yang X, Malik V, Jauch R (2015) Reprogramming cells with synthetic proteins. Asian J Androl 17(3):394–402.  https://doi.org/10.4103/1008-682X.145433 PubMedPubMedCentralGoogle Scholar
  237. 237.
    Tsubooka N, Ichisaka T, Okita K, Takahashi K, Nakagawa M, Yamanaka S (2009) Roles of Sall4 in the generation of pluripotent stem cells from blastocysts and fibroblasts. Genes Cells 14(6):683–694.  https://doi.org/10.1111/j.1365-2443.2009.01301.x PubMedGoogle Scholar
  238. 238.
    Maekawa M, Yamaguchi K, Nakamura T, Shibukawa R, Kodanaka I, Ichisaka T, Kawamura Y, Mochizuki H, Goshima N, Yamanaka S (2011) Direct reprogramming of somatic cells is promoted by maternal transcription factor Glis1. Nature 474(7350):225–229.  https://doi.org/10.1038/nature10106 PubMedGoogle Scholar
  239. 239.
    Wernig M, Meissner A, Cassady JP, Jaenisch R (2008) c-Myc is dispensable for direct reprogramming of mouse fibroblasts. Cell Stem Cell 2(1):10–12.  https://doi.org/10.1016/j.stem.2007.12.001 PubMedGoogle Scholar
  240. 240.
    Feng B, Jiang J, Kraus P, Ng JH, Heng JC, Chan YS, Yaw LP, Zhang W, Loh YH, Han J, Vega VB, Cacheux-Rataboul V, Lim B, Lufkin T, Ng HH (2009) Reprogramming of fibroblasts into induced pluripotent stem cells with orphan nuclear receptor Esrrb. Nat Cell Biol 11(2):197–203.  https://doi.org/10.1038/ncb1827 PubMedGoogle Scholar
  241. 241.
    Maherali N, Hochedlinger K (2009) Tgfbeta signal inhibition cooperates in the induction of iPSCs and replaces Sox2 and cMyc. Curr Biol 19(20):1718–1723.  https://doi.org/10.1016/j.cub.2009.08.025 PubMedPubMedCentralGoogle Scholar
  242. 242.
    Lyssiotis CA, Foreman RK, Staerk J, Garcia M, Mathur D, Markoulaki S, Hanna J, Lairson LL, Charette BD, Bouchez LC, Bollong M, Kunick C, Brinker A, Cho CY, Schultz PG, Jaenisch R (2009) Reprogramming of murine fibroblasts to induced pluripotent stem cells with chemical complementation of Klf4. Proc Natl Acad Sci USA 106(22):8912–8917.  https://doi.org/10.1073/pnas.0903860106 PubMedPubMedCentralGoogle Scholar
  243. 243.
    Kawamura T, Suzuki J, Wang YV, Menendez S, Morera LB, Raya A, Wahl GM, Izpisua Belmonte JC (2009) Linking the p53 tumour suppressor pathway to somatic cell reprogramming. Nature 460(7259):1140–1144.  https://doi.org/10.1038/nature08311 PubMedPubMedCentralGoogle Scholar
  244. 244.
    Chen J, Liu J, Yang J, Chen Y, Chen J, Ni S, Song H, Zeng L, Ding K, Pei D (2011) BMPs functionally replace Klf4 and support efficient reprogramming of mouse fibroblasts by Oct4 alone. Cell Res 21(1):205–212.  https://doi.org/10.1038/cr.2010.172 PubMedGoogle Scholar
  245. 245.
    Moon JH, Heo JS, Kim JS, Jun EK, Lee JH, Kim A, Kim J, Whang KY, Kang YK, Yeo S, Lim HJ, Han DW, Kim DW, Oh S, Yoon BS, Scholer HR, You S (2011) Reprogramming fibroblasts into induced pluripotent stem cells with Bmi1. Cell Res 21(9):1305–1315.  https://doi.org/10.1038/cr.2011.107 PubMedPubMedCentralGoogle Scholar
  246. 246.
    Shi Y, Desponts C, Do JT, Hahm HS, Scholer HR, Ding S (2008) Induction of pluripotent stem cells from mouse embryonic fibroblasts by Oct4 and Klf4 with small-molecule compounds. Cell Stem Cell 3(5):568–574.  https://doi.org/10.1016/j.stem.2008.10.004 PubMedGoogle Scholar
  247. 247.
    Li Y, Zhang Q, Yin X, Yang W, Du Y, Hou P, Ge J, Liu C, Zhang W, Zhang X, Wu Y, Li H, Liu K, Wu C, Song Z, Zhao Y, Shi Y, Deng H (2011) Generation of iPSCs from mouse fibroblasts with a single gene, Oct4, and small molecules. Cell Res 21(1):196–204.  https://doi.org/10.1038/cr.2010.142 PubMedGoogle Scholar
  248. 248.
    Tsai SY, Bouwman BA, Ang YS, Kim SJ, Lee DF, Lemischka IR, Rendl M (2011) Single transcription factor reprogramming of hair follicle dermal papilla cells to induced pluripotent stem cells. Stem Cells 29(6):964–971.  https://doi.org/10.1002/stem.649 PubMedGoogle Scholar
  249. 249.
    Tsai SY, Clavel C, Kim S, Ang YS, Grisanti L, Lee DF, Kelley K, Rendl M (2010) Oct4 and klf4 reprogram dermal papilla cells into induced pluripotent stem cells. Stem Cells 28(2):221–228.  https://doi.org/10.1002/stem.281 PubMedGoogle Scholar
  250. 250.
    Eminli S, Foudi A, Stadtfeld M, Maherali N, Ahfeldt T, Mostoslavsky G, Hock H, Hochedlinger K (2009) Differentiation stage determines potential of hematopoietic cells for reprogramming into induced pluripotent stem cells. Nat Genet 41(9):968–976.  https://doi.org/10.1038/ng.428 PubMedPubMedCentralGoogle Scholar
  251. 251.
    Sugii S, Kida Y, Kawamura T, Suzuki J, Vassena R, Yin YQ, Lutz MK, Berggren WT, Izpisua Belmonte JC, Evans RM (2010) Human and mouse adipose-derived cells support feeder-independent induction of pluripotent stem cells. Proc Natl Acad Sci USA 107(8):3558–3563.  https://doi.org/10.1073/pnas.0910172106 PubMedPubMedCentralGoogle Scholar
  252. 252.
    Wu T, Wang H, He J, Kang L, Jiang Y, Liu J, Zhang Y, Kou Z, Liu L, Zhang X, Gao S (2011) Reprogramming of trophoblast stem cells into pluripotent stem cells by Oct4. Stem Cells 29(5):755–763.  https://doi.org/10.1002/stem.617 PubMedGoogle Scholar
  253. 253.
    Shi Y, Do JT, Desponts C, Hahm HS, Scholer HR, Ding S (2008) A combined chemical and genetic approach for the generation of induced pluripotent stem cells. Cell Stem Cell 2(6):525–528.  https://doi.org/10.1016/j.stem.2008.05.011 PubMedGoogle Scholar
  254. 254.
    Silva J, Barrandon O, Nichols J, Kawaguchi J, Theunissen TW, Smith A (2008) Promotion of reprogramming to ground state pluripotency by signal inhibition. PLoS Biol 6(10):e253.  https://doi.org/10.1371/journal.pbio.0060253 PubMedPubMedCentralGoogle Scholar
  255. 255.
    Kim JB, Zaehres H, Wu G, Gentile L, Ko K, Sebastiano V, Arauzo-Bravo MJ, Ruau D, Han DW, Zenke M, Scholer HR (2008) Pluripotent stem cells induced from adult neural stem cells by reprogramming with two factors. Nature 454(7204):646–650.  https://doi.org/10.1038/nature07061 PubMedGoogle Scholar
  256. 256.
    Utikal J, Maherali N, Kulalert W, Hochedlinger K (2009) Sox2 is dispensable for the reprogramming of melanocytes and melanoma cells into induced pluripotent stem cells. J Cell Sci 122(Pt 19):3502–3510.  https://doi.org/10.1242/jcs.054783 PubMedPubMedCentralGoogle Scholar
  257. 257.
    Aoi T, Yae K, Nakagawa M, Ichisaka T, Okita K, Takahashi K, Chiba T, Yamanaka S (2008) Generation of pluripotent stem cells from adult mouse liver and stomach cells. Science 321(5889):699–702.  https://doi.org/10.1126/science.1154884 PubMedGoogle Scholar
  258. 258.
    Hanna J, Markoulaki S, Schorderet P, Carey BW, Beard C, Wernig M, Creyghton MP, Steine EJ, Cassady JP, Foreman R, Lengner CJ, Dausman JA, Jaenisch R (2008) Direct reprogramming of terminally differentiated mature B lymphocytes to pluripotency. Cell 133(2):250–264.  https://doi.org/10.1016/j.cell.2008.03.028 PubMedPubMedCentralGoogle Scholar
  259. 259.
    Stadtfeld M, Nagaya M, Utikal J, Weir G, Hochedlinger K (2008) Induced pluripotent stem cells generated without viral integration. Science 322(5903):945–949.  https://doi.org/10.1126/science.1162494 PubMedPubMedCentralGoogle Scholar
  260. 260.
    Tan KY, Eminli S, Hettmer S, Hochedlinger K, Wagers AJ (2011) Efficient generation of iPS cells from skeletal muscle stem cells. PLoS One 6(10):e26406.  https://doi.org/10.1371/journal.pone.0026406 PubMedPubMedCentralGoogle Scholar
  261. 261.
    Lowry WE, Richter L, Yachechko R, Pyle AD, Tchieu J, Sridharan R, Clark AT, Plath K (2008) Generation of human induced pluripotent stem cells from dermal fibroblasts. Proc Natl Acad Sci USA 105(8):2883–2888.  https://doi.org/10.1073/pnas.0711983105 PubMedPubMedCentralGoogle Scholar
  262. 262.
    Park IH, Zhao R, West JA, Yabuuchi A, Huo H, Ince TA, Lerou PH, Lensch MW, Daley GQ (2008) Reprogramming of human somatic cells to pluripotency with defined factors. Nature 451(7175):141–146.  https://doi.org/10.1038/nature06534 PubMedGoogle Scholar
  263. 263.
    Zhao Y, Yin X, Qin H, Zhu F, Liu H, Yang W, Zhang Q, Xiang C, Hou P, Song Z, Liu Y, Yong J, Zhang P, Cai J, Liu M, Li H, Li Y, Qu X, Cui K, Zhang W, Xiang T, Wu Y, Zhao Y, Liu C, Yu C, Yuan K, Lou J, Ding M, Deng H (2008) Two supporting factors greatly improve the efficiency of human iPSC generation. Cell Stem Cell 3(5):475–479.  https://doi.org/10.1016/j.stem.2008.10.002 PubMedGoogle Scholar
  264. 264.
    Huangfu D, Osafune K, Maehr R, Guo W, Eijkelenboom A, Chen S, Muhlestein W, Melton DA (2008) Induction of pluripotent stem cells from primary human fibroblasts with only Oct4 and Sox2. Nat Biotechnol 26(11):1269–1275.  https://doi.org/10.1038/nbt.1502 PubMedGoogle Scholar
  265. 265.
    Aasen T, Raya A, Barrero MJ, Garreta E, Consiglio A, Gonzalez F, Vassena R, Bilic J, Pekarik V, Tiscornia G, Edel M, Boue S, Izpisua Belmonte JC (2008) Efficient and rapid generation of induced pluripotent stem cells from human keratinocytes. Nat Biotechnol 26(11):1276–1284.  https://doi.org/10.1038/nbt.1503 PubMedGoogle Scholar
  266. 266.
    Maherali N, Ahfeldt T, Rigamonti A, Utikal J, Cowan C, Hochedlinger K (2008) A high-efficiency system for the generation and study of human induced pluripotent stem cells. Cell Stem Cell 3(3):340–345.  https://doi.org/10.1016/j.stem.2008.08.003 PubMedPubMedCentralGoogle Scholar
  267. 267.
    Yan X, Qin H, Qu C, Tuan RS, Shi S, Huang GT (2010) iPS cells reprogrammed from human mesenchymal-like stem/progenitor cells of dental tissue origin. Stem Cells Dev 19(4):469–480.  https://doi.org/10.1089/scd.2009.0314 PubMedPubMedCentralGoogle Scholar
  268. 268.
    Li H, Collado M, Villasante A, Strati K, Ortega S, Canamero M, Blasco MA, Serrano M (2009) The Ink4/Arf locus is a barrier for iPS cell reprogramming. Nature 460(7259):1136–1139.  https://doi.org/10.1038/nature08290 PubMedPubMedCentralGoogle Scholar
  269. 269.
    Zhao HX, Li Y, Jin HF, Xie L, Liu C, Jiang F, Luo YN, Yin GW, Li Y, Wang J, Li LS, Yao YQ, Wang XH (2010) Rapid and efficient reprogramming of human amnion-derived cells into pluripotency by three factors OCT4/SOX2/NANOG. Differentiation 80(2–3):123–129.  https://doi.org/10.1016/j.diff.2010.03.002 PubMedGoogle Scholar
  270. 270.
    Haase A, Olmer R, Schwanke K, Wunderlich S, Merkert S, Hess C, Zweigerdt R, Gruh I, Meyer J, Wagner S, Maier LS, Han DW, Glage S, Miller K, Fischer P, Scholer HR, Martin U (2009) Generation of induced pluripotent stem cells from human cord blood. Cell Stem Cell 5(4):434–441.  https://doi.org/10.1016/j.stem.2009.08.021 PubMedGoogle Scholar
  271. 271.
    Giorgetti A, Montserrat N, Aasen T, Gonzalez F, Rodriguez-Piza I, Vassena R, Raya A, Boue S, Barrero MJ, Corbella BA, Torrabadella M, Veiga A, Izpisua Belmonte JC (2009) Generation of induced pluripotent stem cells from human cord blood using OCT4 and SOX2. Cell Stem Cell 5(4):353–357.  https://doi.org/10.1016/j.stem.2009.09.008 PubMedPubMedCentralGoogle Scholar
  272. 272.
    Liu H, Ye Z, Kim Y, Sharkis S, Jang YY (2010) Generation of endoderm-derived human induced pluripotent stem cells from primary hepatocytes. Hepatology 51(5):1810–1819.  https://doi.org/10.1002/hep.23626 PubMedPubMedCentralGoogle Scholar
  273. 273.
    Aoki T, Ohnishi H, Oda Y, Tadokoro M, Sasao M, Kato H, Hattori K, Ohgushi H (2010) Generation of induced pluripotent stem cells from human adipose-derived stem cells without c-MYC. Tissue Eng Part A 16(7):2197–2206.  https://doi.org/10.1089/ten.TEA.2009.0747 PubMedGoogle Scholar
  274. 274.
    Bar-Nur O, Russ HA, Efrat S, Benvenisty N (2011) Epigenetic memory and preferential lineage-specific differentiation in induced pluripotent stem cells derived from human pancreatic islet beta cells. Cell Stem Cell 9(1):17–23.  https://doi.org/10.1016/j.stem.2011.06.007 PubMedGoogle Scholar

Copyright information

© Springer International Publishing AG, part of Springer Nature 2018

Authors and Affiliations

  1. 1.CAS Key Laboratory of Regenerative Biology, Joint School of Life Sciences, Guangzhou Institutes of Biomedicine and HealthChinese Academy of Sciences, Guangzhou Medical UniversityGuangzhouChina
  2. 2.Genome Regulation Laboratory, Guangdong Provincial Key Laboratory of Stem Cell and Regenerative Medicine, South China Institute for Stem Cell Biology and Regenerative Medicine, Guangzhou Institutes of Biomedicine and HealthChinese Academy of SciencesGuangzhouChina

Personalised recommendations