Advertisement

Changing the DNA Landscape: Putting a SPN on Chromatin

Chapter
Part of the Current Topics in Microbiology and Immunology book series (CT MICROBIOLOGY, volume 274)

Abstract

In eukaryotic cells, transcription and replication each occur on DNA templates that are incorporated into nucleosomes. Formation of chromatin generally limits accessibility of specific DNA sequences and inhibits progression of polymerases as they copy information from the DNA. The processes that select sites for initiating either transcription or replication are therefore strongly influenced by factors that modulate the properties of chromatin proteins. Further, in order to elongate their products, both DNA and RNA polymerases must be able to overcome the inhibition presented by chromatin (Lipford and Bell 2001; Workman and Kingston 1998).

One way to adjust the properties of chromatin proteins is to covalently modify them by adding or removing chemical moieties. Both histone and non-histone chromatin proteins are altered by acetylation, methylation, and other changes, and the ‘nucleosome modifying’ complexes that perform these reactions are important components of pathways of transcriptional regulation (Cote 2002; Orphanides and Reinberg 2000; Roth et al. 2001; Strahl and Allis 2000; Workman and Kingston 1998). Another way to alter the effects of nucleosomes is to change the position of the histone octamers relative to specific DNA sequences (Orphanides and Reinberg 2000; Verrijzer 2002; Wang 2002; Workman and Kingston 1998). Since the ability of a sequence to be bound by specific proteins can vary significantly whether the sequence is in the linkers between nucleosomes or at various positions within a nucleosome, ‘nucleosome remodeling’ complexes that rearrange nucleosome positioning are also important regulators of transcription. Since the DNA replication machinery has to encounter many of the same challenges posed by chromatin, it seems likely that modifying and remodeling complexes also act during duplication of the genome, but most of the current information on these factors relates to regulation of transcription.

This chapter describes the factor known variously as FACT in humans, where it promotes elongation of RNA polymerase II on nucleosomal templates in vitro (Orphanides et al. 1998, 1999), Duf in frogs, where it is needed for DNA replication in oocyte extracts (Okuhara et al. 1999), and CP or SPN in yeast, where it is linked in vivo to both transcription and replication (Brewster et al. 2001; Formosa et al. 2001). Like the nucleosome modifying and remodeling complexes, it is broadly conserved among eukaryotes, affects a wide range of processes that utilize chromatin, and directly alters the properties of nucleosomes. However, it does not have nucleosome modifying or standard ATP-dependent remodeling activity, and therefore represents a third class of chromatin modulating factors. It is also presently unique in the extensive connections it displays with both transcription and replication: FACT/DUF/CP/SPN appears to modify nucleosomes in a way that is directly important for the efficient functioning of both RNA polymerases and DNA polymerases. While less is known about the mechanisms it uses to promote its functions than for other factors that affect chromatin, it is clearly an essential part of the complex mixture of activities that modulate access to DNA within chromatin.

Physical and genetic interactions suggest that FACT/DUF/CP/SPN affects multiple pathways within replication and transcription as a member of several distinct complexes. Some of the interactions are easy to assimilate into models for replication or transcription, such as direct binding to DNA polymerase /ga (Wittmeyer and Formosa 1997; Wittmeyer et al. 1999), association with nucleosome modifying complexes (John et al. 2000), and interaction with factors that participate in elongation of RNA Polymerase II (Gavin et al. 2002; Squazzo et al. 2002). Others are more surprising such as an association with the 19S complex that regulates the function of the 20S proteasome (Ferdous et al. 2001; Xu et al. 1995), and the indication that FACT/DUF/CP/SPN can act as a specificity factor for casein kinase II (Keller et al. 2001). This chapter reviews the varied approaches that have each revealed different aspects of the function of FACT/DUF/CP/SPN, and presents a picture of a factor that can both alter nucleosomes and orchestrate the assembly or activity of a broad range of complexes that act upon chromatin.

Keywords

High Mobility Group Histone Gene Transcription Elongation Tandem Affinity Purification Transcription Elongation Factor 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.

Preview

Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.

References

  1. Aravind L, Koonin EV (1998) Eukaryotic transcnption regulators derive from ancient enzymatic domains. Curr Biol 8:RIII–RI13Google Scholar
  2. Bortvin A, Winston F (1996) Evidence that Spt6p controls chromatin structure by a direct interaction with histones. Science 272:1473–1476PubMedCrossRefGoogle Scholar
  3. Brewster NK, Johnston GC, Singer RA (1998) Characterization of the CP complex, an abundant dimer of Cdc68 and Pob3 proteins that regulates yeast transcriptional activation and chromatin repression. J Biol Chern 273:21972–21979CrossRefGoogle Scholar
  4. Brewster NK, Johnston GC, Singer RA (2001) A bipartite yeast SSRPI analog comprised of Pob3 and Nhp6 proteins modulates transcription. Mol Cell Biol 21:3491–3502PubMedCrossRefGoogle Scholar
  5. Burley SK, Roeder RG (1996) Biochemistry and structural biology of transcription factor lID (TFIID). Annu Rev Biochem 65:769–799PubMedCrossRefGoogle Scholar
  6. Bustin M (1999) Regulation of DNA-dependent activities by the functional motifs of the high-mobility-group chromosomal proteins. Mol Cell Biol 19:5237–5246PubMedGoogle Scholar
  7. Chang CH, Luse DS (1997) The H3/H4 tetramer blocks transcript elongation by RNA polymerase II in vitro. J Biol Chern 272:23427–23434CrossRefGoogle Scholar
  8. Chang M, French-Cornay D, Fan HY, Klein H, Denis CL, Jaehning JA (1999) A complex containing RNA polymerase II, Paf1p, Cdc73p, Hpr1p, and Ccr4p plays a role in protein kinase C signaling. Mol Cell Biol 19:1056–1067PubMedGoogle Scholar
  9. Clark-Adams CD, Norris D, Osley MA, Fassler JS, Winston F (1988) Changes in histone gene dosage alter transcription in yeast. Genes Dev 2:150–159PubMedCrossRefGoogle Scholar
  10. Costa PJ, Arndt KM (2000) Synthetic lethal interactions suggest a role for the Saccharomyces cerevisiae rtf1 protein in transcription elongation. Genetics 156:535–547PubMedGoogle Scholar
  11. Costigan C, Kolodrubetz D, Snyder M (1994) NHP6a and NHP6b, which encode HMGl-Iike proteins, are candidates for downstream components of the yeast SLT2 mitogen-activated protein kinase pathway. Mol Cell Biol 14:2391–2403PubMedCrossRefGoogle Scholar
  12. Cote J (2002) The MYST family of histone acetyltransferases. Springer-Verlag, HeidelbergGoogle Scholar
  13. Eisenmann DM, Dollard C, Winston F (1989) SPTI5, the gene encoding the yeast TATA binding factor TFIID, is required for normal transcription initiation in vivo. Cell 58:1183–1191PubMedCrossRefGoogle Scholar
  14. Evans DR, Brewster NK, Xu Q, Rowley A, Altheim BA, Johnston GC, Singer RA (1998) The yeast protein complex containing cdc68 and pob3 mediates core-pro moter repression through the cdc68 N-terminal domain. Genetics 150:1393–1405PubMedGoogle Scholar
  15. Exinger F, Lacroute F (1992) 6-Azauracil inhibition of GTP biosynthesis in Saccharomyces cerevisiae. Curr Genet 22:9–11PubMedCrossRefGoogle Scholar
  16. Ferdous A, Gonzalez F, Sun L, Kodadek T, Johnston SA (2001) The 19S regulatory particle of the proteasome is required for efficient transcription elongation by RNA polymerase II. Mol Cell 7:981–991PubMedCrossRefGoogle Scholar
  17. Formosa T, Eriksson P, Wittmeyer J, Ginn J, Yu Y, Stillman DJ (2001) Sptl6-Pob3 and the HMG protein Nhp6 combine to form the nucleosome-binding factor SPN. Embo J 20:3506–3517PubMedCrossRefGoogle Scholar
  18. Formosa T, Nittis T (1999) Dna2 Mutants Reveal Interaction s with DNA Polymerase α and Ctf4, a Pol α Accessory Factor, and Show That Full Dna2 Helicase Activity Is Not Essential for Growth. Genetics 151:1459–1470PubMedGoogle Scholar
  19. Gavin AC, Bosche M, Krause R, Grandi P, Marzioch M, Bauer A, Schultz J, Rick JM, Michon AM, Cruciat CM, Remor M, Hofert C, Schelder M, Brajenovic M, Ruffner H, Merino A, Klein K, Hudak M, Dickson D, Rudi T, Gnau V, Bauch A, Bastuck S, Huhse B, Leutwein C, Heurtier MA, Copley RR, Edelmann A, Querfurth E, Rybin V, Drewes G, Raida M, Bouwmeester T, Bork P, Seraphin B, Kuster B, Neubauer G, Superti-Furga G (2002) Functional organization of the yeast proteome by systematic analysis of protein complexes. Nature 415:141–147PubMedCrossRefGoogle Scholar
  20. Hartzog GA, Wada T, Handa H, Winston F (1998) Evidence that Spt4, Spt5, and Spt6 control transcription elongation by RNApolymerase II in Saccharomyces cerevisiae. Genes Dev 12:357–369PubMedCrossRefGoogle Scholar
  21. Hirschhorn IN, Brown SA, Clark CD, Winston F (1992) Evidence that SNF2/SWI2 and SNF5activate transcription in yeast by altering chromatin structure. Genes Dev 6:2288–2298PubMedCrossRefGoogle Scholar
  22. Ho Y, Gruhler A, Heilbut A, Bader GD, Moore L, Adams SL, Millar A, Taylor P, Bennett K, Boutilier K, Yang L, Wolting C, Donaldson I, Schandorff S, Shewnarane J, Vo M, Taggart J, Goudreault M, Muskat B, Alfarano C, Dewar D, Lin Z, Michalickova K, Willems AR, Sassi H, Nielsen PA, Rasmussen KJ, Andersen JR, Johansen LE, Hansen LH, Jespersen H, Podtelejnikov A, Nielsen E, Crawford J, Poulsen V, Sorensen BD, Matthiesen J, Hendrickson RC, Gleeson F, Pawson T, Moran MF, Durocher D, Mann M, Hogue CW, Figeys D, Tyers M (2002) Systematic identification of protein complexes in Saccharomyces cerevisiae by mass spectrometry. Nature 415:180–183PubMedCrossRefGoogle Scholar
  23. Izban MG, Luse DS (1991) Transcription on nucleosomal templates by RNA polymerase II in vitro: inhibition of elongation with enhancement of sequence-specific pausing. Genes Dev 5:683–696PubMedCrossRefGoogle Scholar
  24. John S, Howe L, Tafrov ST, Grant PA, Sternglanz R, Workman JL (2000) The something about silencing protein, Sas3, is the catalytic subunit of NuA3, a yTAF(II)30-containing HAT complex that interacts with the Spt16 subunit of the yeast CP (Cdc68/Pob3)-FACT complex. Genes Dev 14:1196–1208PubMedGoogle Scholar
  25. Kang SW, Kuzuhara T, Horikoshi M (2000) Functional interaction of general transcription initiation factor TFIIE with general chromatin factor SPTI6/CDC68. Genes Cells 5:251–263PubMedCrossRefGoogle Scholar
  26. Keller DM, Zeng X, Wang Y, Zhang QH, Kapoor M, Shu H, Goodman R, Lozano G, Zhao Y, Lu H (2001) ADNAdamage-induced p53 serine 392 kinase complex contains CK2,hSptl6, and SSRPI. Mol Cell 7:283–292PubMedCrossRefGoogle Scholar
  27. Lipford JR, Bell SP (2001) Nucleosomes positioned by ORCfacilitate the initiation of DNAreplication. Mol Cell 7:21–30PubMedCrossRefGoogle Scholar
  28. Lycan D, Mikesell G, Bunger M, Breeden L (1994) Differential effects of Cdc68 on cell cycle-regulated promoters in Saccharomyces cerevisiae. Mol Cell Biol 14:7455–7465PubMedGoogle Scholar
  29. Malone EA, Clark CD, Chiang A, Winston F (1991) Mutation in SPT161CDC68 suppress cis-and trans-acting mutations that affect promoter function in Saccharomyces cerevisiae. Mol Cell Biol 11:5710–5717PubMedGoogle Scholar
  30. Miles J, Formosa T (1992a) Evidence that POB1,a Saccharomyces cerevisiae protein that binds to DNA polymerase a, acts in DNA metabolism in vivo. Mol Cell Biol 12:5724–5735PubMedGoogle Scholar
  31. Miles J, Formosa T (1992b) Protein affinity chromatography with purified yeast DNA polymerase α detects proteins that bind to DNA polymerase. Proc Nat! Acad Sci USA 89:1276–1280PubMedCrossRefGoogle Scholar
  32. Newport J (1987) Nuclear reconstitution in vitro: stages of assembly around proteinfree DNA. Cell 48:205–217PubMedCrossRefGoogle Scholar
  33. Okuhara K, Ohta K, Seo H, Shioda M, Yamada T, Tanaka Y, Dohmae N, Seyama Y, Shibata T, Murofushi H (1999) A DNAunwinding factor involved in DNAreplication in cell-free extracts of xenopus eggs. Curr Biol 9:341–350PubMedCrossRefGoogle Scholar
  34. Orphanides G, Leroy G, Chang C-H, Luse DS, Reinberg D (1998) FACT, a factor that facilitates transcript elongation through nucleosomes. Cell 92:105116CrossRefGoogle Scholar
  35. Orphanides G, Reinberg D (2000) RNA polymerase II elongation through chromatin. Nature 407:471–475PubMedCrossRefGoogle Scholar
  36. Orphanides G, Wu WH, Lane WS, Hampsey M, Reinberg D (1999) The chromatinspecific transcription elongation factor FACT comprises the human SPT16/CDC68 and SSRP1 proteins. Nature 400:284–288PubMedCrossRefGoogle Scholar
  37. Paull TT, Carey M, Johnson RC (1996) Yeast HMG proteins NHP6A/B potentiate promoter-specific transcriptional activation in vivo and assembly of preinitiation complexes in vitro. Genes Dev 10:2769–2781PubMedCrossRefGoogle Scholar
  38. Powell W, Reines D (1996) Mutations in the second largest subunit of RNA polymerase II cause 6-azauracil sensitivity in yeast and increased transcriptional arrest in vitro. J BiolChern 271:6866–6873Google Scholar
  39. Prendergast JA, Murray LE, Rowley A, Carruthers DR, Singer RA, Johnston GC (1990) Size selection identifies new genes that regulate Saccharomyces cerevisiae cell proliferation. Genetics 124:81–90PubMedGoogle Scholar
  40. Roth SY, Denu JM, Allis CD (2001) Histone acetyltransferases. Annu Rev Biochem 70:81–120PubMedCrossRefGoogle Scholar
  41. Rowley A, Singer RA, Johnston G (1991) CDC68, a yeast gene that affects regulation of cell proliferation and transcription, encodes a protein with a highly acidic carboxyl terminus. Mol Cell Biol 11:5718–5726PubMedGoogle Scholar
  42. Rubin DM, Coux O, Wefes I, Hengartner C, Young RA, Goldberg AL, Finley D (1996) Identification of the ga14 suppressor Sugl as a subunit of the yeast 26S proteasorne. Nature 379:655–657PubMedCrossRefGoogle Scholar
  43. Schlesinger MB, Formosa T (2000) POB3 is required for both transcription and replication in the yeast Saccharomyces cerevisiae. Genetics 155:1593–1606PubMedGoogle Scholar
  44. Schnell R, D’ari L, Foss M, Goodman D, Rine J (1989) Genetic and molecular characterization of suppressors of SIR4 mutations in Saccharomyces cerevisiae. Genetics 122:29–46PubMedGoogle Scholar
  45. Shaw RJ, Reines D (2000) Saccharomyces cerevisiae transcription elongation mutants are defective in PUR5 induction in response to nucleotide depletion. Mol Cell Biol 20:7427–7437PubMedCrossRefGoogle Scholar
  46. Shi X, Chang M, Wolf AJ, Chang CH, Frazer-Abel AA, Wade PA, Burton ZF, Jaehning JA (1997) Cdc73p and Pafl p are found in a novel RNA polymerase I1containing complex distinct from the Srbp-containing holoenzyme. Mol Cell Biol 17:1160–1169PubMedGoogle Scholar
  47. Sidorova J, Breeden L (1999) The MSNI and NHP6A genes suppress SWI6 defects in Saccharomyces cerevisiae. Genetics 151:45–55PubMedGoogle Scholar
  48. Squazzo SL, Costa PJ, Lindstrom D, Kumer KE, Simic R, Jennings JL, Link AJ, Arndt KM, Hartzog G (2002) The Pafl complex physically and functionally associates with transcription elongation factors in vivo. EMBOJ. In PressGoogle Scholar
  49. Strahl BD, Allis CD (2000) The language of covalent histone modifications. Nature 403:41–45PubMedCrossRefGoogle Scholar
  50. Strahl-Bolsinger S, Hecht A, Luo K, Grunstein M (1997) SIR2 and SIR4 interactions differ in core and extended telomeric heterochromatin in yeast. Genes Dev 11:83–93PubMedCrossRefGoogle Scholar
  51. Verma R, Chen S, Feldman R, Schieltz D, Yates J, Dohmen J, Deshaies RJ (2000) Proteasomal proteomics: identification of nucleotide-sensitive proteasome-interacting proteins by mass spectrometric analysis of affinity-purified proteasomes. Mol Biol Cell 11:3425–3439PubMedGoogle Scholar
  52. Verrijzer CP (2002) Gene Regulation by SWIISNF Related Chromatin Remodeling Factors. Springer-Verlag, HeidelbergGoogle Scholar
  53. Voges D, Zwickl P, Baumeister W (1999) The 26S proteasome: a molecular machine designed for controlled proteolysis. Annu Rev Biochem 68:1015–1068PubMedCrossRefGoogle Scholar
  54. Wada T, Orphanides G, Hasegawa J, Kim DK, Shima D, Yamaguchi Y, Fukuda A, Hisatake K, Oh S, Reinberg D, Handa H (2000) FACT relieves DSIF/NELF-mediated inhibition of transcriptional elongation and reveals functional differences between P-TEFb and TFIIH. Mol Cell 5:1067–1072PubMedCrossRefGoogle Scholar
  55. Wada T, Takagi T, Yamaguchi Y, Ferdous A, Imai T, Hirose S, Sugimoto S, Yano K, Hartzog GA, Winston F, Buratowski S, Handa H (1998) DSIF, a novel transcription elongation factor that regulates RNApolymerase II processivity, is composed of human Spt4 and Spt5 homologs. Genes Dev 12:343–356PubMedCrossRefGoogle Scholar
  56. Wang W (2002) The SWIISNF family of ATP-dependent chromatin remodelers: similar mechanisms but diverse functions. Springer-Verlag, HeidelbergGoogle Scholar
  57. Weinert T (1998) DNA damage and checkpoint pathways: molecular anatomy and interactions with repair. Cell 94:555–558PubMedCrossRefGoogle Scholar
  58. White CL, Suto RK, Luger K (2001) Structure of the yeast nucleosome core particle reveals fundamental changes in internucleosome interactions. Embo J 20:5207–5218PubMedCrossRefGoogle Scholar
  59. Winston F (1992) Analysis of SPT genes: A genetic approach towards analysis of TFIID, histones, and other transcription factors of yeast. In McKnight SL and Yamamoto KR (eds.), Transcriptional Regulation. Cold Spring Harbor Laboratory Press, Plainview, NY, pp. 1271–1293Google Scholar
  60. Winston F, Carlson M (1992) Yeast SNF/SWI transcriptional activators and the SPT/SIN chromatin connection. Trends Genet 8:387–391PubMedGoogle Scholar
  61. Winston F, Chaleff DT, Valent B, Fink GR (1984) Mutations affecting Ty-mediated expression of the HIS4 gene of Saccharomyces cerevisiae. Genetics 107:179–197PubMedGoogle Scholar
  62. Wittmeyer J, Formosa T (1997) The Saccharomyces cerevisiae DNA polymerase alpha catalytic subunit interacts with Cdc68/Sptl6 and with Pobs, a protein similar to an HMGl-Iike protein. Mol Cell Biol 17:4178–4190PubMedGoogle Scholar
  63. Wittmeyer J, Joss L, Formosa T (1999) Spt16 and Pob3 of Saccharomyces cerevisiae form an essential) abundant heterodimer that is nuclear) chromatin-associated) and copurifies with DNApolymerase alpha. Biochemistry 38:8961–8971PubMedCrossRefGoogle Scholar
  64. Workman JL, Kingston RE (1998) Alteration of nucleosome structure as a mechanism of Transcriptional Regulation. Annu Rev Biochem 67:545–579PubMedCrossRefGoogle Scholar
  65. Xu Q, Johnston GC, Singer RA (1993) The Saccharomyces cerevisiae Cdc68 transcription activator is antagonized by Sanl, a protein implicated in transcriptional silencing. Mol Cell Biol 13:7553–7565PubMedGoogle Scholar
  66. Xu Q, Singer RA, Johnston GC (1995) Sugl modulates yeast transcription activation by Cdc68. Mol and Cell Biol 15:6025–6035Google Scholar
  67. Yarnell AT, Oh S, Reinberg D, Lippard SJ (2001) Interaction of FACT) SSRPl) and the high mobility group (HMG) domain of SSRPI with DNA damaged by the anticancer drug cisplatin. J Biol Chern 276:25736–25741CrossRefGoogle Scholar
  68. Yu Y, Eriksson P, Stillman DJ (2000) Architectural transcription factors and the SAGA complex function in parallel pathways to activate transcription. Mol Cell Biol 20:2350–2357PubMedCrossRefGoogle Scholar

Copyright information

© Springer-Verlag Berlin Heidelberg 2003

Authors and Affiliations

  1. 1.University of Utah, BiochemistrySalt Lake CityUSA

Personalised recommendations