How Many Non-coding RNAs Does It Take to Compensate Male/Female Genetic Imbalance?

Part of the Advances in Experimental Medicine and Biology book series (AEMB, volume 886)


Genetic sex determination in mammals relies on dimorphic sex chromosomes that confer phenotypic/physiologic differences between males and females. In this heterogametic system, X and Y chromosomes diverged from an ancestral pair of autosomes, creating a genetic disequilibrium between XX females and XY males. Dosage compensation mechanisms alleviate intrinsic gene dosage imbalance, leading to equal expression levels of most X-linked genes in the two sexes. In therian mammals, this is achieved through inactivation of one of the two X chromosomes in females. Failure to undergo X-chromosome inactivation (XCI) results in developmental arrest and death. Although fundamental for survival, a surprising loose conservation in the mechanisms to achieve XCI during development in therian lineage has been, and continues, to be uncovered. XCI involves the concerted action of non-coding RNAs (ncRNAs), including the well-known Xist RNA, and has thus become a classical paradigm to study the mode of action of this particular class of transcripts. In this chapter, we will describe the processes coping with sex chromosome genetic imbalance and how ncRNAs underlie dosage compensation mechanisms and influence male-female differences in mammals. Moreover, we will discuss how ncRNAs have been tinkered with during therian evolution to adapt XCI mechanistic to species-specific constraints.


Dosage compensation X-chromosome inactivation Xist Tsix Sex chromosomes 


  1. Agrelo R, Souabni A, Novatchkova M, Haslinger C, Leeb M, Komnenovic V, Kishimoto H, Gresh L, Kohwi-Shigematsu T, Kenner L, Wutz A (2009) SATB1 defines the developmental context for gene silencing by Xist in lymphoma and embryonic cells. Dev Cell 16(4):507–516PubMedPubMedCentralCrossRefGoogle Scholar
  2. Al Nadaf S, Waters PD, Koina E, Deakin JE, Jordan KS, Graves JA (2010) Activity map of the tammar X chromosome shows that marsupial X inactivation is incomplete and escape is stochastic. Genome Biol 11(12):R122PubMedPubMedCentralCrossRefGoogle Scholar
  3. Anguera MC, Ma W, Clift D, Namekawa S, Kelleher RJ 3rd, Lee JT (2011) Tsx produces a long noncoding RNA and has general functions in the germline, stem cells, and brain. PLoS Genet 7(9):e1002248PubMedPubMedCentralCrossRefGoogle Scholar
  4. Augui S, Filion GJ, Huart S, Nora E, Guggiari M, Maresca M, Stewart AF, Heard E (2007) Sensing X chromosome pairs before X inactivation via a novel X-pairing region of the Xic. Science 318(5856):1632–1636PubMedCrossRefGoogle Scholar
  5. Augui S, Nora EP, Heard E (2011) Regulation of X-chromosome inactivation by the X-inactivation centre. Nat Rev Genet 12(6):429–442PubMedCrossRefGoogle Scholar
  6. Barakat TS, Gunhanlar N, Pardo CG, Achame EM, Ghazvini M, Boers R, Kenter A, Rentmeester E, Grootegoed JA, Gribnau J (2011) RNF12 activates Xist and is essential for X chromosome inactivation. PLoS Genet 7(1):e1002001PubMedPubMedCentralCrossRefGoogle Scholar
  7. Barr ML, Bertram EG (1949) A morphological distinction between neurones of the male and female, and the behaviour of the nucleolar satellite during accelerated nucleoprotein synthesis. Nature 163(4148):676PubMedCrossRefGoogle Scholar
  8. Barr H, Hermann A, Berger J, Tsai HH, Adie K, Prokhortchouk A, Hendrich B, Bird A (2007) Mbd2 contributes to DNA methylation-directed repression of the Xist gene. Mol Cell Biol 27(10):3750–3757PubMedPubMedCentralCrossRefGoogle Scholar
  9. Barton SC, Surani MA, Norris ML (1984) Role of paternal and maternal genomes in mouse development. Nature 311(5984):374–376PubMedCrossRefGoogle Scholar
  10. Beard C, Li E, Jaenisch R (1995) Loss of methylation activates Xist in somatic but not in embryonic cells. Genes Dev 9(19):2325–2334PubMedCrossRefGoogle Scholar
  11. Beletskii A, Hong YK, Pehrson J, Egholm M, Strauss WM (2001) PNA interference mapping demonstrates functional domains in the noncoding RNA Xist. Proc Natl Acad Sci U S A 98(16):9215–9220PubMedPubMedCentralCrossRefGoogle Scholar
  12. Berletch JB, Yang F, Disteche CM (2010) Escape from X inactivation in mice and humans. Genome Biol 11(6):213PubMedPubMedCentralCrossRefGoogle Scholar
  13. Borsani G, Tonlorenzi R, Simmler MC, Dandolo L, Arnaud D, Capra V, Grompe M, Pizzuti A, Muzny D, Lawrence C, Willard HF, Avner P, Ballabio A (1991) Characterization of a murine gene expressed from the inactive X chromosome. Nature 351(6324):325–329PubMedCrossRefGoogle Scholar
  14. Brockdorff N, Ashworth A, Kay GF, Cooper P, Smith S, McCabe VM, Norris DP, Penny GD, Patel D, Rastan S (1991) Conservation of position and exclusive expression of mouse Xist from the inactive X chromosome. Nature 351(6324):329–331PubMedCrossRefGoogle Scholar
  15. Brockdorff N, Ashworth A, Kay GF, McCabe VM, Norris DP, Cooper PJ, Swift S, Rastan S (1992) The product of the mouse Xist gene is a 15 kb inactive X-specific transcript containing no conserved ORF and located in the nucleus. Cell 71(3):515–526PubMedCrossRefGoogle Scholar
  16. Brons IG, Smithers LE, Trotter MW, Rugg-Gunn P, Sun B, Chuva de Sousa Lopes SM, Howlett SK, Clarkson A, Ahrlund-Richter L, Pedersen RA, Vallier L (2007) Derivation of pluripotent epiblast stem cells from mammalian embryos. Nature 448(7150):191–195PubMedCrossRefGoogle Scholar
  17. Brown CJ, Ballabio A, Rupert JL, Lafreniere RG, Grompe M, Tonlorenzi R, Willard HF (1991a) A gene from the region of the human X inactivation centre is expressed exclusively from the inactive X chromosome. Nature 349(6304):38–44PubMedCrossRefGoogle Scholar
  18. Brown CJ, Lafreniere RG, Powers VE, Sebastio G, Ballabio A, Pettigrew AL, Ledbetter DH, Levy E, Craig IW, Willard HF (1991b) Localization of the X inactivation centre on the human X chromosome in Xq13. Nature 349(6304):82–84PubMedCrossRefGoogle Scholar
  19. Brown CJ, Hendrich BD, Rupert JL, Lafreniere RG, Xing Y, Lawrence J, Willard HF (1992) The human XIST gene: analysis of a 17 kb inactive X-specific RNA that contains conserved repeats and is highly localized within the nucleus. Cell 71(3):527–542PubMedCrossRefGoogle Scholar
  20. Burgoyne PS, Thornhill AR, Boudrean SK, Darling SM, Bishop CE, Evans EP (1995) The genetic basis of XX-XY differences present before gonadal sex differentiation in the mouse. Philos Trans R Soc Lond B Biol Sci 350(1333):253–260, discussion 260–251PubMedCrossRefGoogle Scholar
  21. Calabrese JM, Sun W, Song L, Mugford JW, Williams L, Yee D, Starmer J, Mieczkowski P, Crawford GE, Magnuson T (2012) Site-specific silencing of regulatory elements as a mechanism of X inactivation. Cell 151(5):951–963PubMedPubMedCentralCrossRefGoogle Scholar
  22. Chaumeil J, Le Baccon P, Wutz A, Heard E (2006) A novel role for Xist RNA in the formation of a repressive nuclear compartment into which genes are recruited when silenced. Genes Dev 20(16):2223–2237PubMedPubMedCentralCrossRefGoogle Scholar
  23. Chen X, McClusky R, Itoh Y, Reue K, Arnold AP (2013) X and Y chromosome complement influence adiposity and metabolism in mice. Endocrinology 154(3):1092–1104PubMedPubMedCentralCrossRefGoogle Scholar
  24. Chureau C, Prissette M, Bourdet A, Barbe V, Cattolico L, Jones L, Eggen A, Avner P, Duret L (2002) Comparative sequence analysis of the X-inactivation center region in mouse, human, and bovine. Genome Res 12(6):894–908PubMedPubMedCentralGoogle Scholar
  25. Chureau C, Chantalat S, Romito A, Galvani A, Duret L, Avner P, Rougeulle C (2010) Ftx is a non-coding RNA which affects Xist expression and chromatin structure within the X-inactivation center region. Hum Mol Genet 20(4):705–718PubMedCrossRefGoogle Scholar
  26. Chuva de Sousa Lopes SM, Hayashi K, Shovlin TC, Mifsud W, Surani MA, McLaren A (2008) X chromosome activity in mouse XX primordial germ cells. PLoS Genet 4(2):e30PubMedPubMedCentralCrossRefGoogle Scholar
  27. Clemson CM, McNeil JA, Willard HF, Lawrence JB (1996) XIST RNA paints the inactive X chromosome at interphase: evidence for a novel RNA involved in nuclear/chromosome structure. J Cell Biol 132(3):259–275PubMedCrossRefGoogle Scholar
  28. Cohen DE, Davidow LS, Erwin JA, Xu N, Warshawsky D, Lee JT (2007) The DXPas34 repeat regulates random and imprinted X inactivation. Dev Cell 12(1):57–71PubMedCrossRefGoogle Scholar
  29. de Napoles M, Mermoud JE, Wakao R, Tang YA, Endoh M, Appanah R, Nesterova TB, Silva J, Otte AP, Vidal M, Koseki H, Brockdorff N (2004) Polycomb group proteins Ring1A/B link ubiquitylation of histone H2A to heritable gene silencing and X inactivation. Dev Cell 7(5):663–676PubMedCrossRefGoogle Scholar
  30. De Vries GJ, Rissman EF, Simerly RB, Yang LY, Scordalakes EM, Auger CJ, Swain A, Lovell-Badge R, Burgoyne PS, Arnold AP (2002) A model system for study of sex chromosome effects on sexually dimorphic neural and behavioral traits. J Neurosci 22(20):9005–9014PubMedGoogle Scholar
  31. Deng X, Hiatt JB, Nguyen DK, Ercan S, Sturgill D, Hillier LW, Schlesinger F, Davis CA, Reinke VJ, Gingeras TR, Shendure J, Waterston RH, Oliver B, Lieb JD, Disteche CM (2011) Evidence for compensatory upregulation of expressed X-linked genes in mammals, caenorhabditis elegans and drosophila melanogaster. Nat Genet 43(12):1179–1185PubMedPubMedCentralCrossRefGoogle Scholar
  32. Dewing P, Shi T, Horvath S, Vilain E (2003) Sexually dimorphic gene expression in mouse brain precedes gonadal differentiation. Brain Res Mol Brain Res 118(1–2):82–90PubMedCrossRefGoogle Scholar
  33. Dindot SV, Kent KC, Evers B, Loskutoff N, Womack J, Piedrahita JA (2004) Conservation of genomic imprinting at the XIST, IGF2, and GTL2 loci in the bovine. Mamm Genome 15(12):966–974PubMedCrossRefGoogle Scholar
  34. Dupont C, Gribnau J (2013) Different flavors of X-chromosome inactivation in mammals. Curr Opin Cell Biol 25(3):314–321PubMedCrossRefGoogle Scholar
  35. Duret L, Chureau C, Samain S, Weissenbach J, Avner P (2006) The Xist RNA gene evolved in eutherians by pseudogenization of a protein-coding gene. Science 312(5780):1653–1655PubMedCrossRefGoogle Scholar
  36. Elisaphenko EA, Kolesnikov NN, Shevchenko AI, Rogozin IB, Nesterova TB, Brockdorff N, Zakian SM (2008) A dual origin of the Xist gene from a protein-coding gene and a set of transposable elements. PLoS One 3(6):e2521PubMedPubMedCentralCrossRefGoogle Scholar
  37. Engreitz JM, Pandya-Jones A, McDonel P, Shishkin A, Sirokman K, Surka C, Kadri S, Xing J, Goren A, Lander ES, Plath K, Guttman M (2013) The Xist lncRNA exploits three-dimensional genome architecture to spread across the X chromosome. Science 341(6147):1237973PubMedPubMedCentralCrossRefGoogle Scholar
  38. Gontan C, Achame EM, Demmers J, Barakat TS, Rentmeester E, van IW, Grootegoed JA, Gribnau J (2012) RNF12 initiates X-chromosome inactivation by targeting REX1 for degradation. Nature 485(7398):386–390PubMedCrossRefGoogle Scholar
  39. Grant J, Mahadevaiah SK, Khil P, Sangrithi MN, Royo H, Duckworth J, McCarrey JR, VandeBerg JL, Renfree MB, Taylor W, Elgar G, Camerini-Otero RD, Gilchrist MJ, Turner JM (2012) Rsx is a metatherian RNA with Xist-like properties in X-chromosome inactivation. Nature 487(7406):254–258PubMedPubMedCentralCrossRefGoogle Scholar
  40. Graves JA (2010) Review: sex chromosome evolution and the expression of sex-specific genes in the placenta. Placenta 31(Suppl):S27–S32PubMedCrossRefGoogle Scholar
  41. Hasegawa Y, Brockdorff N, Kawano S, Tsutui K, Nakagawa S (2010) The matrix protein hnRNP U is required for chromosomal localization of Xist RNA. Dev Cell 19(3):469–476PubMedCrossRefGoogle Scholar
  42. Heard E, Rougeulle C, Arnaud D, Avner P, Allis CD, Spector DL (2001) Methylation of histone H3 at Lys-9 is an early mark on the X chromosome during X inactivation. Cell 107(6):727–738PubMedCrossRefGoogle Scholar
  43. Hendriksen PJ, Hoogerbrugge JW, Themmen AP, Koken MH, Hoeijmakers JH, Oostra BA, van der Lende T, Grootegoed JA (1995) Postmeiotic transcription of X and Y chromosomal genes during spermatogenesis in the mouse. Dev Biol 170(2):730–733PubMedCrossRefGoogle Scholar
  44. Hosler BA, LaRosa GJ, Grippo JF, Gudas LJ (1989) Expression of REX-1, a gene containing zinc finger motifs, is rapidly reduced by retinoic acid in F9 teratocarcinoma cells. Mol Cell Biol 9(12):5623–5629PubMedPubMedCentralCrossRefGoogle Scholar
  45. Jeon Y, Lee JT (2011) YY1 tethers Xist RNA to the inactive X nucleation center. Cell 146(1):119–133PubMedPubMedCentralCrossRefGoogle Scholar
  46. Johnston CM, Newall AE, Brockdorff N, Nesterova TB (2002) Enox, a novel gene that maps 10 kb upstream of Xist and partially escapes X inactivation. Genomics 80(2):236–244PubMedCrossRefGoogle Scholar
  47. Jonkers I, Barakat TS, Achame EM, Monkhorst K, Kenter A, Rentmeester E, Grosveld F, Grootegoed JA, Gribnau J (2009) RNF12 is an X-Encoded dose-dependent activator of X chromosome inactivation. Cell 139(5):999–1011PubMedCrossRefGoogle Scholar
  48. Koina E, Chaumeil J, Greaves IK, Tremethick DJ, Graves JA (2009) Specific patterns of histone marks accompany X chromosome inactivation in a marsupial. Chromosome Res 17(1):115–126PubMedCrossRefGoogle Scholar
  49. Lee JT (2000) Disruption of imprinted X inactivation by parent-of-origin effects at Tsix. Cell 103(1):17–27PubMedCrossRefGoogle Scholar
  50. Lee JT, Lu N (1999) Targeted mutagenesis of Tsix leads to nonrandom X inactivation. Cell 99(1):47–57PubMedCrossRefGoogle Scholar
  51. Lee JT, Davidow LS, Warshawsky D (1999) Tsix, a gene antisense to Xist at the X-inactivation centre. Nat Genet 21(4):400–404PubMedCrossRefGoogle Scholar
  52. Luikenhuis S, Wutz A, Jaenisch R (2001) Antisense transcription through the Xist locus mediates Tsix function in embryonic stem cells. Mol Cell Biol 21(24):8512–8520PubMedPubMedCentralCrossRefGoogle Scholar
  53. Lyon MF (1961) Gene action in the X-chromosome of the mouse (Mus musculus L.). Nature 190:372–373PubMedCrossRefGoogle Scholar
  54. Mahadevaiah SK, Royo H, VandeBerg JL, McCarrey JR, Mackay S, Turner JM (2009) Key features of the X inactivation process are conserved between marsupials and eutherians. Curr Biol 19(17):1478–1484PubMedCrossRefGoogle Scholar
  55. Mak W, Nesterova TB, de Napoles M, Appanah R, Yamanaka S, Otte AP, Brockdorff N (2004) Reactivation of the paternal X chromosome in early mouse embryos. Science 303(5658):666–669PubMedCrossRefGoogle Scholar
  56. Makhlouf M, Rougeulle C (2011) Linking X chromosome inactivation to pluripotency: necessity or fate? Trends Mol Med 17(6):329–336PubMedCrossRefGoogle Scholar
  57. Marahrens Y, Panning B, Dausman J, Strauss W, Jaenisch R (1997) Xist-deficient mice are defective in dosage compensation but not spermatogenesis. Genes Dev 11(2):156–166PubMedCrossRefGoogle Scholar
  58. Masui O, Bonnet I, Le Baccon P, Brito I, Pollex T, Murphy N, Hupe P, Barillot E, Belmont AS, Heard E (2011) Live-cell chromosome dynamics and outcome of X chromosome pairing events during ES cell differentiation. Cell 145(3):447–458PubMedPubMedCentralCrossRefGoogle Scholar
  59. McGrath J, Solter D (1984) Completion of mouse embryogenesis requires both the maternal and paternal genomes. Cell 37(1):179–183PubMedCrossRefGoogle Scholar
  60. Migeon BR, Chowdhury AK, Dunston JA, McIntosh I (2001) Identification of TSIX, encoding an RNA antisense to human XIST, reveals differences from its murine counterpart: implications for X inactivation. Am J Hum Genet 69(5):951–960PubMedPubMedCentralCrossRefGoogle Scholar
  61. Minkovsky A, Barakat TS, Sellami N, Chin MH, Gunhanlar N, Gribnau J, Plath K (2013) The pluripotency factor-bound intron 1 of Xist is dispensable for X chromosome inactivation and reactivation in vitro and in vivo. Cell Rep 3(3):905–918PubMedPubMedCentralCrossRefGoogle Scholar
  62. Monk M, Harper MI (1979) Sequential X chromosome inactivation coupled with cellular differentiation in early mouse embryos. Nature 281(5729):311–313PubMedCrossRefGoogle Scholar
  63. Moreira de Mello JC, de Araujo ES, Stabellini R, Fraga AM, de Souza JE, Sumita DR, Camargo AA, Pereira LV (2010) Random X inactivation and extensive mosaicism in human placenta revealed by analysis of allele-specific gene expression along the X chromosome. PLoS One 5(6):e10947PubMedPubMedCentralCrossRefGoogle Scholar
  64. Mueller JL, Mahadevaiah SK, Park PJ, Warburton PE, Page DC, Turner JM (2008) The mouse X chromosome is enriched for multicopy testis genes showing postmeiotic expression. Nat Genet 40(6):794–799PubMedPubMedCentralCrossRefGoogle Scholar
  65. Navarro P, Pichard S, Ciaudo C, Avner P, Rougeulle C (2005) Tsix transcription across the Xist gene alters chromatin conformation without affecting Xist transcription: implications for X-chromosome inactivation. Genes Dev 19(12):1474–1484PubMedPubMedCentralCrossRefGoogle Scholar
  66. Navarro P, Page DR, Avner P, Rougeulle C (2006) Tsix-mediated epigenetic switch of a CTCF-flanked region of the Xist promoter determines the Xist transcription program. Genes Dev 20(20):2787–2792PubMedPubMedCentralCrossRefGoogle Scholar
  67. Navarro P, Chambers I, Karwacki-Neisius V, Chureau C, Morey C, Rougeulle C, Avner P (2008) Molecular coupling of Xist regulation and pluripotency. Science 321(5896):1693–1695PubMedCrossRefGoogle Scholar
  68. Navarro P, Oldfield A, Legoupi J, Festuccia N, Dubois A, Attia M, Schoorlemmer J, Rougeulle C, Chambers I, Avner P (2010) Molecular coupling of Tsix regulation and pluripotency. Nature 468(7322):457–460PubMedCrossRefGoogle Scholar
  69. Nechanitzky R, Davila A, Savarese F, Fietze S, Grosschedl R (2012) Satb1 and Satb2 are dispensable for X chromosome inactivation in mice. Dev Cell 23(4):866–871PubMedCrossRefGoogle Scholar
  70. Nora EP, Lajoie BR, Schulz EG, Giorgetti L, Okamoto I, Servant N, Piolot T, van Berkum NL, Meisig J, Sedat J, Gribnau J, Barillot E, Bluthgen N, Dekker J, Heard E (2012) Spatial partitioning of the regulatory landscape of the X-inactivation centre. Nature 485(7398):381–385PubMedPubMedCentralCrossRefGoogle Scholar
  71. Ohhata T, Hoki Y, Sasaki H, Sado T (2006) Tsix-deficient X chromosome does not undergo inactivation in the embryonic lineage in males: implications for Tsix-independent silencing of Xist. Cytogenet Genome Res 113(1–4):345–349PubMedCrossRefGoogle Scholar
  72. Ohhata T, Hoki Y, Sasaki H, Sado T (2008) Crucial role of antisense transcription across the Xist promoter in Tsix-mediated Xist chromatin modification. Development 135(2):227–235PubMedCrossRefGoogle Scholar
  73. Ohno S, Kaplan WD, Kinosita R (1959) Formation of the sex chromatin by a single X-chromosome in liver cells of rattus norvegicus. Exp Cell Res 18:415–418PubMedCrossRefGoogle Scholar
  74. Okamoto I, Otte AP, Allis CD, Reinberg D, Heard E (2004) Epigenetic dynamics of imprinted X inactivation during early mouse development. Science 303(5658):644–649PubMedCrossRefGoogle Scholar
  75. Okamoto I, Patrat C, Thepot D, Peynot N, Fauque P, Daniel N, Diabangouaya P, Wolf JP, Renard JP, Duranthon V, Heard E (2011) Eutherian mammals use diverse strategies to initiate X-chromosome inactivation during development. Nature 472(7343):370–374PubMedCrossRefGoogle Scholar
  76. Panning B, Jaenisch R (1996) DNA hypomethylation can activate Xist expression and silence X-linked genes. Genes Dev 10(16):1991–2002PubMedCrossRefGoogle Scholar
  77. Pelton TA, Sharma S, Schulz TC, Rathjen J, Rathjen PD (2002) Transient pluripotent cell populations during primitive ectoderm formation: correlation of in vivo and in vitro pluripotent cell development. J Cell Sci 115(Pt 2):329–339PubMedGoogle Scholar
  78. Penny GD, Kay GF, Sheardown SA, Rastan S, Brockdorff N (1996) Requirement for Xist in X chromosome inactivation. Nature 379(6561):131–137PubMedCrossRefGoogle Scholar
  79. Peters AH, Mermoud JE, O’Carroll D, Pagani M, Schweizer D, Brockdorff N, Jenuwein T (2002) Histone H3 lysine 9 methylation is an epigenetic imprint of facultative heterochromatin. Nat Genet 30(1):77–80PubMedCrossRefGoogle Scholar
  80. Plath K, Fang J, Mlynarczyk-Evans SK, Cao R, Worringer KA, Wang H, de la Cruz CC, Otte AP, Panning B, Zhang Y (2003) Role of histone H3 lysine 27 methylation in X inactivation. Science 300(5616):131–135PubMedCrossRefGoogle Scholar
  81. Pullirsch D, Hartel R, Kishimoto H, Leeb M, Steiner G, Wutz A (2010) The trithorax group protein Ash2l and Saf-A are recruited to the inactive X chromosome at the onset of stable X inactivation. Development 137(6):935–943PubMedPubMedCentralCrossRefGoogle Scholar
  82. Rasmussen TP, Mastrangelo MA, Eden A, Pehrson JR, Jaenisch R (2000) Dynamic relocalization of histone MacroH2A1 from centrosomes to inactive X chromosomes during X inactivation. J Cell Biol 150(5):1189–1198PubMedPubMedCentralCrossRefGoogle Scholar
  83. Rastan S (1982) Timing of X-chromosome inactivation in post-implantation mouse embryos. J Embryol Exp Morphol 71:11–24PubMedGoogle Scholar
  84. Rastan S (1983) Non-random X-chromosome inactivation in mouse X-autosome translocation embryos – location of the inactivation centre. J Embryol Exp Morphol 78:1–22PubMedGoogle Scholar
  85. Rastan S, Brown SD (1990) The search for the mouse X-chromosome inactivation centre. Genet Res 56(2–3):99–106PubMedCrossRefGoogle Scholar
  86. Ray PF, Winston RM, Handyside AH (1997) XIST expression from the maternal X chromosome in human male preimplantation embryos at the blastocyst stage. Hum Mol Genet 6(8):1323–1327PubMedCrossRefGoogle Scholar
  87. Rogers MB, Hosler BA, Gudas LJ (1991) Specific expression of a retinoic acid-regulated, zinc-finger gene, Rex-1, in preimplantation embryos, trophoblast and spermatocytes. Development 113(3):815–824PubMedGoogle Scholar
  88. Rougeulle C, Chaumeil J, Sarma K, Allis CD, Reinberg D, Avner P, Heard E (2004) Differential histone H3 Lys-9 and Lys-27 methylation profiles on the X chromosome. Mol Cell Biol 24(12):5475–5484PubMedPubMedCentralCrossRefGoogle Scholar
  89. Sado T, Wang Z, Sasaki H, Li E (2001) Regulation of imprinted X-chromosome inactivation in mice by Tsix. Development 128(8):1275–1286PubMedGoogle Scholar
  90. Sado T, Li E, Sasaki H (2002) Effect of Tsix disruption on Xist expression in male ES cells. Cytogenet Genome Res 99(1–4):115–118PubMedGoogle Scholar
  91. Sado T, Okano M, Li E, Sasaki H (2004) De novo DNA methylation is dispensable for the initiation and propagation of X chromosome inactivation. Development 131(5):975–982PubMedCrossRefGoogle Scholar
  92. Sarma K, Levasseur P, Aristarkhov A, Lee JT (2010) Locked nucleic acids (LNAs) reveal sequence requirements and kinetics of Xist RNA localization to the X chromosome. Proc Natl Acad Sci U S A 107(51):22196–22201PubMedPubMedCentralCrossRefGoogle Scholar
  93. Savarese F, Flahndorfer K, Jaenisch R, Busslinger M, Wutz A (2006) Hematopoietic precursor cells transiently reestablish permissiveness for X inactivation. Mol Cell Biol 26(19):7167–7177PubMedPubMedCentralCrossRefGoogle Scholar
  94. Shao C, Takagi N (1990) An extra maternally derived X chromosome is deleterious to early mouse development. Development 110(3):969–975PubMedGoogle Scholar
  95. Shibata S, Lee JT (2004) Tsix transcription- versus RNA-based mechanisms in Xist repression and epigenetic choice. Curr Biol 14(19):1747–1754PubMedCrossRefGoogle Scholar
  96. Shin J, Bossenz M, Chung Y, Ma H, Byron M, Taniguchi-Ishigaki N, Zhu X, Jiao B, Hall LL, Green MR, Jones SN, Hermans-Borgmeyer I, Lawrence JB, Bach I (2010) Maternal Rnf12/RLIM is required for imprinted X-chromosome inactivation in mice. Nature 467(7318):977–981PubMedPubMedCentralCrossRefGoogle Scholar
  97. Simmler MC, Cunningham DB, Clerc P, Vermat T, Caudron B, Cruaud C, Pawlak A, Szpirer C, Weissenbach J, Claverie JM, Avner P (1996) A 94 kb genomic sequence 3′ to the murine Xist gene reveals an AT rich region containing a new testis specific gene Tsx. Hum Mol Genet 5(11):1713–1726PubMedCrossRefGoogle Scholar
  98. Solari AJ (1974) The behavior of the XY pair in mammals. Int Rev Cytol 38:273–317PubMedCrossRefGoogle Scholar
  99. Spencer RJ, del Rosario BC, Pinter SF, Lessing D, Sadreyev RI, Lee JT (2011) A boundary element between Tsix and Xist binds the chromatin insulator Ctcf and contributes to initiation of X-chromosome inactivation. Genetics 189(2):441–454PubMedPubMedCentralCrossRefGoogle Scholar
  100. Stavropoulos N, Rowntree RK, Lee JT (2005) Identification of developmentally specific enhancers for Tsix in the regulation of X chromosome inactivation. Mol Cell Biol 25(7):2757–2769PubMedPubMedCentralCrossRefGoogle Scholar
  101. Sugimoto M, Abe K (2007) X chromosome reactivation initiates in nascent primordial germ cells in mice. PLoS Genet 3(7):e116PubMedPubMedCentralCrossRefGoogle Scholar
  102. Sun BK, Deaton AM, Lee JT (2006) A transient heterochromatic state in Xist preempts X inactivation choice without RNA stabilization. Mol Cell 21(5):617–628PubMedCrossRefGoogle Scholar
  103. Sun S, Fukue Y, Nolen L, Sadreyev R, Lee JT (2011) Characterization of Xpr (Xpct) reveals instability but no effects on X-chromosome pairing or Xist expression. Transcription 1(1):46–56CrossRefGoogle Scholar
  104. Sun S, Del Rosario BC, Szanto A, Ogawa Y, Jeon Y, Lee JT (2013) Jpx RNA activates Xist by evicting CTCF. Cell 153(7):1537–1551PubMedPubMedCentralCrossRefGoogle Scholar
  105. Takagi N, Sasaki M (1975) Preferential inactivation of the paternally derived X chromosome in the extraembryonic membranes of the mouse. Nature 256(5519):640–642PubMedCrossRefGoogle Scholar
  106. Takagi N, Sugawara O, Sasaki M (1982) Regional and temporal changes in the pattern of X-chromosome replication during the early post-implantation development of the female mouse. Chromosoma 85(2):275–286PubMedCrossRefGoogle Scholar
  107. Tam PP, Zhou SX, Tan SS (1994) X-chromosome activity of the mouse primordial germ cells revealed by the expression of an X-linked lacZ transgene. Development 120(10):2925–2932PubMedGoogle Scholar
  108. Tan SS, Williams EA, Tam PP (1993) X-chromosome inactivation occurs at different times in different tissues of the post-implantation mouse embryo. Nat Genet 3(2):170–174PubMedCrossRefGoogle Scholar
  109. Tian D, Sun S, Lee JT (2010) The long noncoding RNA, Jpx, is a molecular switch for X chromosome inactivation. Cell 143(3):390–403PubMedPubMedCentralCrossRefGoogle Scholar
  110. Turner JM (2007) Meiotic sex chromosome inactivation. Development 134(10):1823–1831PubMedCrossRefGoogle Scholar
  111. Turner JM, Mahadevaiah SK, Elliott DJ, Garchon HJ, Pehrson JR, Jaenisch R, Burgoyne PS (2002) Meiotic sex chromosome inactivation in male mice with targeted disruptions of Xist. J Cell Sci 115(Pt 21):4097–4105PubMedCrossRefGoogle Scholar
  112. Vallot C, Huret C, Lesecque Y, Resch A, Oudrhiri N, Bennaceur-Griscelli A, Duret L, Rougeulle C (2013) XACT, a long noncoding transcript coating the active X chromosome in human pluripotent cells. Nat Genet 45(3):239–241PubMedCrossRefGoogle Scholar
  113. Vigneau S, Augui S, Navarro P, Avner P, Clerc P (2006) An essential role for the DXPas34 tandem repeat and Tsix transcription in the counting process of X chromosome inactivation. Proc Natl Acad Sci U S A 103(19):7390–7395PubMedPubMedCentralCrossRefGoogle Scholar
  114. Wake N, Takagi N, Sasaki M (1976) Non-random inactivation of X chromosome in the rat yolk sac. Nature 262(5569):580–581PubMedCrossRefGoogle Scholar
  115. Wutz A, Jaenisch R (2000) A shift from reversible to irreversible X inactivation is triggered during ES cell differentiation. Mol Cell 5(4):695–705PubMedCrossRefGoogle Scholar
  116. Wutz A, Rasmussen TP, Jaenisch R (2002) Chromosomal silencing and localization are mediated by different domains of Xist RNA. Nat Genet 30(2):167–174PubMedCrossRefGoogle Scholar
  117. Yen ZC, Meyer IM, Karalic S, Brown CJ (2007) A cross-species comparison of X-chromosome inactivation in eutheria. Genomics 90(4):453–463PubMedCrossRefGoogle Scholar

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© Springer Science+Business Media Dordrecht 2016

Authors and Affiliations

  1. 1.UMR7216 Epigenetics and Cell FateCNRS/Université Paris DiderotParisFrance

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