X Chromosome Inactivation and Embryonic Stem Cells

  • Tahsin Stefan Barakat
  • Joost Gribnau
Part of the Advances in Experimental Medicine and Biology book series (AEMB, volume 695)


X chromosome inactivation (XCI) is a process required to equalize the dosage of X-encoded genes between female and male cells. XCI is initiated very early during female embryonic development or upon differentiation of female embryonic stem (ES) cells and results in inactivation of one X chromosome in every female somatic cell. The regulation of XCI involves factors that also play a crucial role in ES cell maintenance and differentiation and the XCI process therefore provides a beautiful paradigm to study ES cell biology. In this chapter we describe the important cis and trans acting regulators of XCI and introduce the models that have been postulated to explain initiation of XCI in female cells only. We also discuss the proteins involved in the establishment of the inactive X chromosome and describe the different chromatin modifications associated with the inactivation process. Finally, we describe the potential of mouse and human ES and induced pluripotent stem (iPS) cells as model systems to study the XCI process.


Embryonic Stem Cell Human Embryonic Stem Cell Inner Cell Mass Chromosome Inactivation Antisense Transcription 
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.


Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.


  1. 1.
    Ohno S. Sex chromosomes and Sex-linked genes. 1967, Berlin: Springer.Google Scholar
  2. 2.
    Charlesworth B. The evolution of sex chromosomes. Science 1991; 251(4997):1030–3.PubMedGoogle Scholar
  3. 3.
    Graves JA. The origin and function of the mammalian Y chromosome and Y-borne genes—an evolving understanding. Bioessays 1995; 17(4):311–20.PubMedGoogle Scholar
  4. 4.
    Graves JA, Koina E, Sankovic N. How the gene content of human sex chromosomes evolved. Curr Opin Genet Dev 2006; 16(3):219–24.PubMedGoogle Scholar
  5. 5.
    Graves JA. Sex chromosome specialization and degeneration in mammals. Cell 2006; 124(5):901–14.PubMedGoogle Scholar
  6. 6.
    Skaletsky H, Kuroda-Kawaguchi T, Minx PJ et al. The male-specific region of the human Y chromosome is a mosaic of discrete sequence classes. Nature 2003; 423(6942):825–37.PubMedGoogle Scholar
  7. 7.
    Koopman P, Gubbay J, Vivian N et al. Male development of chromosomally female mice transgenic for Sry. Nature 1991; 351(6322):117–21.PubMedGoogle Scholar
  8. 8.
    Ross MT, Grafham DV, Coffey AJ et al. The DNA sequence of the human X chromosome. Nature 2005; 434(7031):325–37.PubMedGoogle Scholar
  9. 9.
    Lyon MF. Gene action in the X-chromosome of the mouse (Mus musculus L.). Nature 1961; 190:372–3.PubMedGoogle Scholar
  10. 10.
    Lyon MF, Phillips RJ, Searle AG. A test for mutagenicity of caffeine in mice. Z Vererbungsl 1962; 93:7–13.PubMedGoogle Scholar
  11. 11.
    Lyon MF. Sex chromatin and gene action in the mammalian X-chromosome. Am J Hum Genet 1962; 14:135–48.PubMedGoogle Scholar
  12. 12.
    Davidson RG, Nitowsky HM, Childs B. Demonstration of two populations of cells in the human female heterozygous for glucose-6-phosphate dehydrogenase variants. Proc Natl Acad Sci USA 1963; 50: 481–5.PubMedGoogle Scholar
  13. 13.
    Adler DA, Rugarli EI, Lingenfelter PA et al. Evidence of evolutionary up-regulation of the single active X chromosome in mammals based on Clc4 expression levels in Mus spretus and Mus musculus. Proc Natl Acad Sci USA 1997; 94(17):9244–8.PubMedGoogle Scholar
  14. 14.
    Birchler JA, Fernandez HR, Kavi HH. Commonalities in compensation. Bioessays 2006; 28(6):565–8.PubMedGoogle Scholar
  15. 15.
    Lin H, Gupta V, Vermilyea MD et al. Dosage compensation in the mouse balances up-regulation and silencing of X-linked genes. PLoS Biol 2007; 5(12):e326.PubMedGoogle Scholar
  16. 16.
    Nguyen DK, Disteche CM. Dosage compensation of the active X chromosome in mammals. Nat Genet 2006; 38(1):47–53.PubMedGoogle Scholar
  17. 17.
    Takagi N, Sasaki M. Preferential inactivation of the paternally derived X chromosome in the extraembryonic membranes of the mouse. Nature 1975; 256(5519):640–2.PubMedGoogle Scholar
  18. 18.
    Huynh KD, Lee JT. Inheritance of a pre-inactivated paternal X chromosome in early mouse embryos. Nature 2003; 426(6968):857–62.PubMedGoogle Scholar
  19. 19.
    Okamoto I, Otte AP, Allis CD et al. Epigenetic dynamics of imprinted X inactivation during early mouse development. Science 2004; 303(5658):644–9.PubMedGoogle Scholar
  20. 20.
    Evans MJ, Kaufman MH. Establishment in culture of pluripotential cells from mouse embryos. Nature 1981; 292(5819):154–6.PubMedGoogle Scholar
  21. 21.
    Martin GR. Isolation of a pluripotent cell line from early mouse embryos cultured in medium conditioned by teratocarcinoma stem cells. Proc Natl Acad Sci USA 1981; 78(12):7634–8.PubMedGoogle Scholar
  22. 22.
    Thomson JA, Itskovitz-Eldor J, Shapiro SS et al. Embryonic stem cell lines derived from human blastocysts. Science 1998; 282(5391):1145–7.PubMedGoogle Scholar
  23. 23.
    Keller G. Embryonic stem cell differentiation: emergence of a new era in biology and medicine. Genes Dev 2005; 19(10):1129–55.PubMedGoogle Scholar
  24. 24.
    Leahy A, Xiong JW, Kuhnert F et al. Use of developmental marker genes to define temporal and spatial patterns of differentiation during embryoid body formation. J Exp Zool 1999; 284(1):67–81.PubMedGoogle Scholar
  25. 25.
    Monk M. A stem-line model for cellular and chromosomal differentiation in early mouse-development. Differentiation 1981; 19(2):71–6.PubMedGoogle Scholar
  26. 26.
    Takahashi K, Yamanaka S. Induction of pluripotent stem cells from mouse embryonic and adult fibroblast cultures by defined factors. Cell 2006; 126(4):663–76.PubMedGoogle Scholar
  27. 27.
    Nakagawa M, Koyanagi M, Tanabe K et al. Generation of induced pluripotent stem cells without Myc from mouse and human fibroblasts. Nat Biotechnol 2008; 26(1):101–6.PubMedGoogle Scholar
  28. 28.
    Wernig M, Meissner A, Foreman R et al. In vitro reprogramming of fibroblasts into a pluripotent ES-cell-like state. Nature 2007; 448(7151):318–24.PubMedGoogle Scholar
  29. 29.
    Yu J, Vodyanik MA, Smuga-Otto K et al. Induced pluripotent stem cell lines derived from human somatic cells. Science 2007; 318(5858):1917–20.PubMedGoogle Scholar
  30. 30.
    Takahashi K, Tanabe K, Ohnuki M et al. Induction of pluripotent stem cells from adult human fibroblasts by defined factors. Cell 2007; 131(5):861–72.PubMedGoogle Scholar
  31. 31.
    Park IH, Zhao R, West JA et al. Reprogramming of human somatic cells to pluripotency with defined factors. Nature 2008; 451(7175):141–6.PubMedGoogle Scholar
  32. 32.
    Maherali N, Sridharan R, Xie W et al. Directly reprogrammed fibroblasts show global epigenetic remodeling and widespread tissue contribution. Cell Stem Cell 2007; 1(1):55–70.PubMedGoogle Scholar
  33. 33.
    Stadtfeld M, Maherali N, Breault DT et al. Defining molecular cornerstones during fibroblast to iPS cell reprogramming in mouse. Cell Stem Cell 2008; 2(3):230–40.PubMedGoogle Scholar
  34. 34.
    Russell LB. Mammalian X-chromosome action: inactivation limited in spread and region of origin. Science 1963; 140:976–8.PubMedGoogle Scholar
  35. 35.
    Rastan S. Non-random X-chromosome inactivation in mouse X-autosome translocation embryos-location of the inactivation centre. J Embryol Exp Morphol 1983; 78:1–22.PubMedGoogle Scholar
  36. 36.
    Rastan S, Robertson EJ. X-chromosome deletions in embryo-derived (EK) cell lines associated with lack of X-chromosome inactivation. J Embryol Exp Morphol 1985; 90:379–88.PubMedGoogle Scholar
  37. 37.
    Brown CJ, Ballabio A, Rupert JL et al. A gene from the region of the human X inactivation centre is expressed exclusively from the inactive X chromosome. Nature 1991; 349(6304):38–44.PubMedGoogle Scholar
  38. 38.
    Heard E, Avner P. Role play in X-inactivation. Hum Mol Genet 1994; 3 Spec No:1481–5.PubMedGoogle Scholar
  39. 39.
    Borsani G, Tonlorenzi R, Simmler MC et al. Characterization of a murine gene expressed from the inactive X chromosome. Nature 1991; 351(6324):325–9.PubMedGoogle Scholar
  40. 40.
    Brockdorff N, Ashworth A, Kay GF et al. Conservation of position and exclusive expression of mouse Xist from the inactive X chromosome. Nature 1991; 351(6324):329–31.PubMedGoogle Scholar
  41. 41.
    Brockdorff N, Ashworth A, Kay GF et al. 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 1992; 71(3):515–26.PubMedGoogle Scholar
  42. 42.
    Brown CJ, Hendrich BD, Rupert JL et al. 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 1992; 71(3):527–42.PubMedGoogle Scholar
  43. 43.
    Clemson CM, McNeil JA, Willard HF et al. XIST RNA paints the inactive X chromosome at interphase: evidence for a novel RNA involved in nuclear/chromosome structure. J Cell Biol 1996; 132(3):259–75.PubMedGoogle Scholar
  44. 44.
    Jonkers I, Monkhorst K, Rentmeester E et al. Xist RNA is confined to the nuclear territory of the silenced X chromosome throughout the cell cycle. Mol Cell Biol 2008; 28(18):5583–94.PubMedGoogle Scholar
  45. 45.
    Penny GD, Kay GF, Sheardown SA et al. Requirement for Xist in X chromosome inactivation. Nature 1996; 379(6561):131–7.PubMedGoogle Scholar
  46. 46.
    Marahrens Y, Panning B, Dausman J et al. Xist-deficient mice are defective in dosage compensation but not spermatogenesis. Genes Dev 1997; 11(2):156–66.PubMedGoogle Scholar
  47. 47.
    Csankovszki G, Panning B, Bates B et al. Conditional deletion of Xist disrupts histone macroH2A localization but not maintenance of X inactivation. Nat Genet 1999; 22(4):323–4.PubMedGoogle Scholar
  48. 48.
    Kay GF, Penny GD, Patel D et al. Expression of Xist during mouse development suggests a role in the initiation of X chromosome inactivation. Cell 1993; 72(2):171–82.PubMedGoogle Scholar
  49. 49.
    Sun BK, Deaton AM, Lee JT. A transient heterochromatic state in Xist preempts X inactivation choice without RNA stabilization. Mol Cell 2006; 21(5):617–28.PubMedGoogle Scholar
  50. 50.
    Plath K, Fang J, Mlynarczyk-Evans SK et al. Role of histone H3 lysine 27 methylation in X inactivation. Science 2003; 300(5616):131–5.PubMedGoogle Scholar
  51. 51.
    Silva J, Mak W, Zvetkova I et al. Establishment of histone h3 methylation on the inactive X chromosome requires transient recruitment of Eed-Enx1 polycomb group complexes. Dev Cell 2003; 4(4):481–95.PubMedGoogle Scholar
  52. 52.
    Zhao J, Sun BK, Erwin JA et al. Polycomb proteins targeted by a short repeat RNA to the mouse X chromosome. Science 2008; 322(5902):750–6.PubMedGoogle Scholar
  53. 53.
    Lee JT, Davidow LS, Warshawsky D. Tsix, a gene antisense to Xist at the X-inactivation centre. Nat Genet 1999; 21(4):400–4.PubMedGoogle Scholar
  54. 54.
    Lee JT, Lu N. Targeted mutagenesis of Tsix leads to nonrandom X inactivation. Cell 1999; 99(1):47–57.PubMedGoogle Scholar
  55. 55.
    Clerc P, Avner P. Role of the region 3’ to Xist exon 6 in the counting process of X-chromosome inactivation. Nat Genet 1998; 19(3):249–53.PubMedGoogle Scholar
  56. 56.
    Shibata S, Lee JT. Characterization and quantitation of differential Tsix transcripts: implications for Tsix function. Hum Mol Genet 2003; 12(2):125–36.PubMedGoogle Scholar
  57. 57.
    Marks H, Chow JC, Denissov S et al. High-resolution analysis of epigenetic changes associated with X inactivation. Genome Res 2009; 19(8):1361–73.PubMedGoogle Scholar
  58. 58.
    Luikenhuis S, Wutzand A, Jaenisch R. Antisense transcription through the Xist locus mediates Tsix function in embryonic stem cells. Mol Cell Biol 2001; 21(24):8512–20.PubMedGoogle Scholar
  59. 59.
    Navarro P, Pichard S, Ciaudo C et al. Tsix transcription across the Xist gene alters chromatin conformation without affecting Xist transcription: implications for X-chromosome inactivation. Genes Dev 2005; 19(12):1474–84.PubMedGoogle Scholar
  60. 60.
    Vigneau S, Augui S, Navarro P et al. An essential role for the DXPas34 tandem repeat and Tsix transcription in the counting process of X chromosome inactivation. Proc Natl Acad Sci USA 2006; 103(19):7390–5.Google Scholar
  61. 61.
    Ohhata T, Hoki Y, Sasaki H et al. Crucial role of antisense transcription across the Xist promoter in Tsix-mediated Xist chromatin modification. Development 2008; 135(2):227–35.PubMedGoogle Scholar
  62. 62.
    Cohen DE, Davidow LS, Erwin JA et al. The DXPas34 repeat regulates random and imprinted X inactivation. Dev Cell 2007; 12(1):57–71.PubMedGoogle Scholar
  63. 63.
    Debrand E, Chureau C, Arnaud D et al. Functional analysis of the DXPas34 locus, a 3’ regulator of Xist expression. Mol Cell Biol 1999; 19(12):8513–25.PubMedGoogle Scholar
  64. 64.
    Prissette M, El-Maarri O, Arnaud D et al. Methylation profiles of DXPas34 during the onset of X-inactivation. Hum Mol Genet 2001; 10(1):31–8.PubMedGoogle Scholar
  65. 65.
    Boumil RM, Ogawa Y, Sun BK et al. Differential methylation of Xite and CTCF sites in Tsix mirrors the pattern of X-inactivation choice in mice. Mol Cell Biol 2006; 26(6):2109–17.Google Scholar
  66. 66.
    Ogawa Y, Sun BK, Lee JT. Intersection of the RNA interference and X-inactivation pathways. Science 2008; 320(5881):1336–41.PubMedGoogle Scholar
  67. 67.
    Nesterova TB, Popova BC, Cobb BS et al. Dicer regulates Xist promoter methylation in ES cells indirectly through transcriptional control of Dnmt3a. Epigenetics Chromatin 2008; 1(1):2.PubMedGoogle Scholar
  68. 68.
    Kanellopoulou C, Muljo SA, Dimitrov SD et al. X chromosome inactivation in the absence of Dicer. Proc Natl Acad Sci USA 2009; 106(4):1122–7.PubMedGoogle Scholar
  69. 69.
    Shibata S Lee JT. Tsix transcription-versus RNA-based mechanisms in Xist repression and epigenetic choice. Curr Biol 2004; 14(19):1747–54.PubMedGoogle Scholar
  70. 70.
    Ogawa Y, Lee JT. Xite, X-inactivation intergenic transcription elements that regulate the probability of choice. Mol Cell 2003; 11(3):731–43.PubMedGoogle Scholar
  71. 71.
    Stavropoulos N, Rowntree RK, Lee JT. Identification of developmentally specific enhancers for Tsix in the regulation of X chromosome inactivation. Mol Cell Biol 2005; 25(7):2757–69.PubMedGoogle Scholar
  72. 72.
    Chao W, Huynh KD, Spencer RJ et al. CTCF, a candidate trans-acting factor for X-inactivation choice. Science 2002; 295(5553):345–7.PubMedGoogle Scholar
  73. 73.
    Donohoe ME, Zhang LF, Xu N et al. Identification of a Ctcf cofactor, Yy1, for the X chromosome binary switch. Mol Cell 2007; 25(1):43–56.PubMedGoogle Scholar
  74. 74.
    Donohoe ME, Silva SS, Pinter SF et al. The pluripotency factor Oct4 interacts with Ctcf and also controls X-chromosome pairing and counting. Nature 2009; 460(7251):128–32.PubMedGoogle Scholar
  75. 75.
    Chambers I, Colby D, Robertson M et al. Functional expression cloning of Nanog, a pluripotency sustaining factor in embryonic stem cells. Cell 2003; 113(5):643–55.PubMedGoogle Scholar
  76. 76.
    Mitsui K, Tokuzawa Y, Itoh H et al. The homeoprotein Nanog is required for maintenance of pluripotency in mouse epiblast and ES cells. Cell 2003; 113(5):631–42.PubMedGoogle Scholar
  77. 77.
    Nichols J, Zevnik B, Anastassiadis K et al. Formation of pluripotent stem cells in the mammalian embryo depends on the POU transcription factor Oct4. Cell 1998; 95(3):379–91.PubMedGoogle Scholar
  78. 78.
    Avilion AA, Nicolis SK, Pevny LH et al. Multipotent cell lineages in early mouse development depend on SOX2 function. Genes Dev 2003; 17(1):126–40.PubMedGoogle Scholar
  79. 79.
    Navarro P, Chambers I, Karwacki-Neisius V et al. Molecular coupling of Xist regulation and pluripotency. Science 2008; 321(5896):1693–5.PubMedGoogle Scholar
  80. 80.
    Silva J, Nichols J, Theunissen TW et al. Nanog is the gateway to the pluripotent ground state. Cell 2009; 138(4):722–37.PubMedGoogle Scholar
  81. 81.
    Jonkers I, Barakat TS, Achame EM et al. RNF12 is an X-Encoded dose-dependent activator of X chromosome inactivation. Cell 2009; 139(5):999–1011.PubMedGoogle Scholar
  82. 82.
    Bach I, Rodriguez-Esteban C, Carrière C et al. RLIM inhibits functional activity of LIM homeodomain transcription factors via recruitment of the histone deacetylase complex. Nat Genet 1999; 22(4):394–9.PubMedGoogle Scholar
  83. 83.
    Her YR, Chung IK. Ubiquitin Ligase RLIM Modulates Telomere Length Homeostasis through a Proteolysis of TRF1. J Biol Chem 2009; 284(13):8557–66.PubMedGoogle Scholar
  84. 84.
    JJohnsen SA, Güngör C, Prenzel T et al. Regulation of estrogen-dependent transcription by the LIM cofactors CLIM and RLIM in breast cancer. Cancer Res 2009; 69(1):128–36.PubMedGoogle Scholar
  85. 85.
    Jacobs Pa, Baikie Ag, Brown Wm et al. Evidence for the existence of the human “super female”. Lancet 1959; 2(7100):423–5.PubMedGoogle Scholar
  86. 86.
    Maclean N, Mitchell JM. A survey of sex-chromosome abnormalities among 4514 mental defectives. Lancet 1962; 1(7224):293–6.PubMedGoogle Scholar
  87. 87.
    Grumbach MM, Morishima A, Taylor JH. Human Sex Chromosome Abnormalities in Relation to DNA Replication and Heterochromatinization. Proc Natl Acad Sci USA 1963; 49(5):581–9.PubMedGoogle Scholar
  88. 88.
    Carr DH. Chromosome studies in selected spontaneous abortions. 1. Conception after oral contraceptives. Can Med Assoc J 1970; 103(4):343–8.PubMedGoogle Scholar
  89. 89.
    Webb S, de Vries TJ, Kaufman MH. The differential staining pattern of the X chromosome in the embryonic and extraembryonic tissues of postimplantation homozygous tetraploid mouse embryos. Genet Res 1992; 59(3):205–14.PubMedGoogle Scholar
  90. 90.
    Harnden DG. Nuclear sex in triploid XXY human cells. Lancet 1961; 2(7200):488.PubMedGoogle Scholar
  91. 91.
    Nicodemi M, Prisco A. Symmetry-breaking model for X-chromosome inactivation. Phys Rev Lett 2007; 98(10):108104.PubMedGoogle Scholar
  92. 92.
    Nicodemi M, Prisco A. Self-assembly and DNA binding of the blocking factor in x chromosome inactivation. PLoS Comput Biol 2007; 3(11):e210.PubMedGoogle Scholar
  93. 93.
    Lee JT, Strauss WM, Dausman JA et al. A 450 kb transgene displays properties of the mammalian X-inactivation center. Cell 1996; 86(1):83–94.PubMedGoogle Scholar
  94. 94.
    Herzing LB, Romer JT, Horn JM et al. Xist has properties of the X-chromosome inactivation centre. Nature 1997; 386(6622):272–5.PubMedGoogle Scholar
  95. 95.
    Lee JT, Jaenisch R. Long-range cis effects of ectopic X-inactivation centres on a mouse autosome. Nature 1997; 386(6622):275–9.PubMedGoogle Scholar
  96. 96.
    Lee JT, Lu N, Han Y. Genetic analysis of the mouse X inactivation center defines an 80-kb multifunction domain. Proc Natl Acad Sci USA 1999; 96(7):3836–41.PubMedGoogle Scholar
  97. 97.
    Migeon BR, Kazi E, Haisley-Royster C et al. Human X inactivation center induces random X chromosome inactivation in male transgenic mice. Genomics 1999; 59(2):113–21.PubMedGoogle Scholar
  98. 98.
    Migeon BR, Winter H, Kazi E et al. Low-copy-number human transgene is recognized as an X inactivation center in mouse ES cells, but fails to induce cis-inactivation in chimeric mice. Genomics 2001; 71(2):156–62.PubMedGoogle Scholar
  99. 99.
    Heard E, Kress C, Mongelard F et al. Transgenic mice carrying an Xist-containing YAC. Hum Mol Genet 1996; 5(4):441–50.PubMedGoogle Scholar
  100. 100.
    Matsuura S, Episkopou V, Hamvas R et al. Xist expression from an Xist YAC transgene carried on the mouse Y chromosome. Hum Mol Genet 1996; 5(4):451–9.PubMedGoogle Scholar
  101. 101.
    Heard E, Mongelard F, Arnaud D et al. Xist yeast artificial chromosome transgenes function as X-inactivation centers only in multicopy arrays and not as single copies. Mol Cell Biol 1999; 19(4):3156–66.PubMedGoogle Scholar
  102. 102.
    Gribnau J et al. X chromosome choice occurs independently of asynchronous replication timing. J Cell Biol 2005; 168(3):365–73.PubMedGoogle Scholar
  103. 103.
    Marahrens Y, Loring J, Jaenisch R. Role of the Xist gene in X chromosome choosing. Cell 1998; 92(5):657–64.PubMedGoogle Scholar
  104. 104.
    Nesterova TB, Johnston CM, Appanah R et al. Skewing X chromosome choice by modulating sense transcription across the Xist locus. Genes Dev 2003; 17(17):2177–90.PubMedGoogle Scholar
  105. 105.
    Sado T, Li E, Sasaki H. Effect of TSIX disruption on XIST expression in male ES cells. Cytogenet Genome Res 2002; 99(1–4):115–8.PubMedGoogle Scholar
  106. 106.
    Monkhorst K, Jonkers I, Rentmeester E et al. X inactivation counting and choice is a stochastic process: evidence for involvement of an X-linked activator. Cell 2008; 132(3):410–21.PubMedGoogle Scholar
  107. 107.
    Lee JT. Homozygous Tsix mutant mice reveal a sex-ratio distortion and revert to random X-inactivation. Nat Genet 2002; 32(1):195–200.PubMedGoogle Scholar
  108. 108.
    Mlynarczyk-Evans S, Royce-Tolland M, Alexander MK et al. X chromosomes alternate between two states prior to random X-inactivation. PLoS Biol 2006; 4(6):e159.PubMedGoogle Scholar
  109. 109.
    Bacher CP, Guggiari M, Brors B et al. Transient colocalization of X-inactivation centres accompanies the initiation of X inactivation. Nat Cell Biol 2006; 8(3):293–9.PubMedGoogle Scholar
  110. 110.
    Xu N, Tsai CL, Lee JT. Transient homologous chromosome pairing marks the onset of X inactivation. Science 2006; 311(5764):1149–52.PubMedGoogle Scholar
  111. 111.
    Xu N, Donohoe ME, Silva SS et al. Evidence that homologous X-chromosome pairing requires transcription and Ctcf protein. Nat Genet 2007; 39(11):1390–6.PubMedGoogle Scholar
  112. 112.
    Augui S, Filion GJ, Huart S et al. Sensing X chromosome pairs before X inactivation via a novel X-pairing region of the Xic. Science 2007; 318(5856):1632–6.PubMedGoogle Scholar
  113. 113.
    Takagi N. Variable X chromosome inactivation patterns in near-tetraploid murine EC x somatic cell hybrid cells differentiated in vitro. Genetica 1993; 88(2–3):107–17.PubMedGoogle Scholar
  114. 114.
    Monkhorst K, de Hoon B, Jonkers I et al. The probability to initiate X chromosome inactivation is determined by the X to autosomal ratio and X chromosome specific allelic properties. PLoS One 2009; 4(5):e5616.PubMedGoogle Scholar
  115. 115.
    Barr ML, Bertram EG. A morphological distinction between neurones of the male and female and the behaviour of the nucleolar satellite during accelerated nucleoprotein synthesis. Nature 1949; 163(4148):676.PubMedGoogle Scholar
  116. 116.
    Ohno S, Hauschka TS. Allocycly of the X-chromosome in tumors and normal tissues. Cancer Res 1960; 20:541–5.PubMedGoogle Scholar
  117. 117.
    Wutz A, Rasmussen TP, Jaenisch R. Chromosomal silencing and localization are mediated by different domains of Xist RNA. Nat Genet 2002; 30(2):167–74.PubMedGoogle Scholar
  118. 118.
    Chaumeil J, Le Baccon P, Wutz A et al. A novel role for Xist RNA in the formation of a repressive nuclear compartment into which genes are recruited when silenced. Genes Dev 2006; 20(16):2223–37.PubMedGoogle Scholar
  119. 119.
    Clemson CM, Hall LL, Byron M et al. The X chromosome is organized into a gene-rich outer rim and an internal core containing silenced nongenic sequences. Proc Natl Acad Sci USA 2006; 103(20):7688–93.PubMedGoogle Scholar
  120. 120.
    Goto Y, Gomez M, Brockdorff N et al. Differential patterns of histone methylation and acetylation distinguish active and repressed alleles at X-linked genes. Cytogenet Genome Res 2002; 99(1–4):66–74.PubMedGoogle Scholar
  121. 121.
    Heard E, Rougeulle C, Arnaud D et al. Methylation of histone H3 at Lys-9 is an early mark on the X chromosome during X inactivation. Cell 2001; 107(6):727–38.PubMedGoogle Scholar
  122. 122.
    Mak W, Baxter J, Silva J et al. Mitotically stable association of polycomb group proteins eed and enx1 with the inactive x chromosome in trophoblast stem cells. Curr Biol 2002; 12(12):1016–20.PubMedGoogle Scholar
  123. 123.
    Boggs BA, Cheung P, Heard E et al. Differentially methylated forms of histone H3 show unique association patterns with inactive human X chromosomes. Nat Genet 2002; 30(1):73–6.PubMedGoogle Scholar
  124. 124.
    Mermoud JE, Popova B, Peters AH et al. Histone H3 lysine 9 methylation occurs rapidly at the onset of random X chromosome inactivation. Curr Biol 2002; 12(3):247–51.PubMedGoogle Scholar
  125. 125.
    Peters AH, Mermoud JE, O’Carroll D et al. Histone H3 lysine 9 methylation is an epigenetic imprint of facultative heterochromatin. Nat Genet 2002; 30(1):77–80.PubMedGoogle Scholar
  126. 126.
    Rougeulle C, Chaumeil J, Sarma K et al. Differential histone H3 Lys-9 and Lys-27 methylation profiles on the X chromosome. Mol Cell Biol 2004; 24(12):5475–84.PubMedGoogle Scholar
  127. 127.
    Kohlmaier A, Savarese F, Lachner M et al. A chromosomal memory triggered by Xist regulates histone methylation in X inactivation. PLoS Biol 2004; 2(7):E171.PubMedGoogle Scholar
  128. 128.
    Costanzi C, Pehrson JR. Histone macroH2A1 is concentrated in the inactive X chromosome of female mammals. Nature 1998; 393(6685):599–601.PubMedGoogle Scholar
  129. 129.
    Lock LF, Takagi N, Martin GR. Methylation of the Hprt gene on the inactive X occurs after chromosome inactivation. Cell 1987; 48(1):39–46.PubMedGoogle Scholar
  130. 130.
    Norris DP, Brockdorff N, Rastan S. Methylation status of CpG-rich islands on active and inactive mouse X chromosomes. Mamm Genome 1991; 1(2):78–83.PubMedGoogle Scholar
  131. 131.
    Mohandas T, Sparkes RS, Shapiro LJ. Reactivation of an inactive human X chromosome: evidence for X inactivation by DNA methylation. Science 1981; 211(4480):393–6.PubMedGoogle Scholar
  132. 132.
    Russell LB, Montgomery CS. Comparative studies on X-autosome translocations in the mouse. II. Inactivation of autosomal loci, segregation and mapping of autosomal breakpoints in five T (X;1) S. Genetics 1970; 64(2):281–312.PubMedGoogle Scholar
  133. 133.
    Duthie SM, Nesterova TB, Formstone EJ et al. Xist RNA exhibits a banded localization on the inactive X chromosome and is excluded from autosomal material in cis. Hum Mol Genet 1999; 8(2):195–204.PubMedGoogle Scholar
  134. 134.
    Keohane AM et al. H4 acetylation, XIST RNA and replication timing are coincident and define x; autosome boundaries in two abnormal X chromosomes. Hum Mol Genet 1999; 8(2):377–83.PubMedGoogle Scholar
  135. 135.
    Popova BC, Tada T, Takagi N et al. Attenuated spread of X-inactivation in an X; autosome translocation. Proc Natl Acad Sci USA 2006; 103(20):7706–11.PubMedGoogle Scholar
  136. 136.
    Gartler SM, Riggs AD. Mammalian X-chromosome inactivation. Annu Rev Genet 1983; 17:155–90.PubMedGoogle Scholar
  137. 137.
    Lyon MF. X-chromosome inactivation: a repeat hypothesis. Cytogenet Cell Genet 1998; 80(1–4):133–7.PubMedGoogle Scholar
  138. 138.
    Lyon MF. LINE-1 elements and X chromosome inactivation: a function for “junk” DNA? Proc Natl Acad Sci USA 2000; 97(12):6248–9.PubMedGoogle Scholar
  139. 139.
    Lyon MF. Do LINEs Have a Role in X-Chromosome Inactivation? J Biomed Biotechnol 2006; 2006(1):59746.PubMedGoogle Scholar
  140. 140.
    Lyon MF. No longer ‘all-or-none’. Eur J Hum Genet 2005; 13(7):796–7.PubMedGoogle Scholar
  141. 141.
    Furano AV. The biological properties and evolutionary dynamics of mammalian LINE-1 retrotransposons. Prog Nucleic Acid Res Mol Biol 2000; 64:255–94.PubMedGoogle Scholar
  142. 142.
    Waters PD, Dobigny G, Pardini AT et al. LINE-1 distribution in Afrotheria and Xenarthra: implications for understanding the evolution of LINE-1 in eutherian genomes. Chromosoma 2004; 113(3):137–44.PubMedGoogle Scholar
  143. 143.
    Parish DA, Vise P, Wichman HA et al. Distribution of LINEs and other repetitive elements in the karyotype of the bat Carollia: implications for X-chromosome inactivation. Cytogenet Genome Res 2002; 96(1–4):191–7.PubMedGoogle Scholar
  144. 144.
    Wichman HA, Van den Bussche RA, Hamilton MJ et al. Transposable elements and the evolution of genome organization in mammals. Genetica 1992; 86(1–3):287–93.PubMedGoogle Scholar
  145. 145.
    Bailey JA, Carrel L, Chakravarti A et al. Molecular evidence for a relationship between LINE-1 elements and X chromosome inactivation: the Lyon repeat hypothesis. Proc Natl Acad Sci USA 2000; 97(12):6634–9.PubMedGoogle Scholar
  146. 146.
    Carrel L, Willard HF. X-inactivation profile reveals extensive variability in X-linked gene expression in females. Nature 2005; 434(7031):400–4.PubMedGoogle Scholar
  147. 147.
    Wang Z, Willard HF, Mukherjee S et al. Evidence of influence of genomic DNA sequence on human X chromosome inactivation. PLoS Comput Biol 2006; 2(9):e113.PubMedGoogle Scholar
  148. 148.
    Hall LL, Clemson CM, Byron M et al. Unbalanced X; autosome translocations provide evidence for sequence specificity in the association of XIST RNA with chromatin. Hum Mol Genet 2002; 11(25):3157–65.PubMedGoogle Scholar
  149. 149.
    Sharp AJ, Spotswood HT, Robinson DO et al. Molecular and cytogenetic analysis of the spreading of X inactivation in X; autosome translocations. Hum Mol Genet 2002; 11(25):3145–56.PubMedGoogle Scholar
  150. 150.
    Sharp A, Robinson DO, Jacobs P. Absence of correlation between late-replication and spreading of X inactivation in an X; autosome translocation. Hum Genet 2001; 109(3):295–302.PubMedGoogle Scholar
  151. 151.
    White WM, Willard HF, Van Dyke DL et al. The spreading of X inactivation into autosomal material of an x; autosome translocation: evidence for a difference between autosomal and X-chromosomal DNA. Am J Hum Genet 1998; 63(1):20–8.PubMedGoogle Scholar
  152. 152.
    Solari AJ, Rahn IM, Ferreyra ME et al. The behavior of sex chromosomes in two human X-autosome translocations: failure of extensive X-inactivation spreading. Biocell 2001; 25(2):155–66.PubMedGoogle Scholar
  153. 153.
    Dobigny G, Ozouf-Costaz C, Bonillo C et al. Viability of X-autosome translocations in mammals: an epigenomic hypothesis from a rodent case-study. Chromosoma 2004; 113(1):34–41.PubMedGoogle Scholar
  154. 154.
    Chureau C, Prissette M, Bourdet A et al. Comparative sequence analysis of the X-inactivation center region in mouse, human and bovine. Genome Res 2002; 12(6):894–908.PubMedGoogle Scholar
  155. 155.
    Cantrell MA, Carstens BC, Wichman HA. X chromosome inactivation and Xist evolution in a rodent lacking LINE-1 activity. PLoS One 2009; 4(7):e6252.PubMedGoogle Scholar
  156. 156.
    Ke X, Collins A. CpG islands in human X-inactivation. Ann Hum Genet 2003; 67(Pt 3):242–9.PubMedGoogle Scholar
  157. 157.
    Cao R, Zhang Y. SUZ12 is required for both the histone methyltransferase activity and the silencing function of the EED-EZH2 complex. Mol Cell 2004; 15(1):57–67.PubMedGoogle Scholar
  158. 158.
    de la Cruz CC, Fang J, Plath K et al. Developmental regulation of Suz 12 localization. Chromosoma 2005; 114(3):183–92.PubMedGoogle Scholar
  159. 159.
    Wang J, Mager J, Chen Y et al. Imprinted X inactivation maintained by a mouse Polycomb group gene. Nat Genet 2001; 28(4):371–5.PubMedGoogle Scholar
  160. 160.
    Kalantry S, Magnuson T. The Polycomb group protein EED is dispensable for the initiation of random X-chromosome inactivation. PLoS Genet 2006; 2(5):e66.PubMedGoogle Scholar
  161. 161.
    Schoeftner S, Sengupta AK, Kubicek S et al. Recruitment of PRC1 function at the initiation of X inactivation independent of PRC2 and silencing. EMBO J 2006; 25(13):3110–22.PubMedGoogle Scholar
  162. 162.
    de Napoles M, Mermoud JE, Wakao R et al. Polycomb group proteins Ring1A/B link ubiquitylation of histone H2A to heritable gene silencing and X inactivation. Dev Cell 2004; 7(5):663–76.PubMedGoogle Scholar
  163. 163.
    Fang J, Chen T, Chadwick B et al. Ring1b-mediated H2A ubiquitination associates with inactive X chromosomes and is involved in initiation of X inactivation. J Biol Chem 2004; 279(51):52812–5.PubMedGoogle Scholar
  164. 164.
    Hernández-Muñoz I, Lund AH, van der Stoop P et al. Stable X chromosome inactivation involves the PRC1 Polycomb complex and requires histone MACROH2A1 and the CULIN3/SPOP ubiquitin E3 ligase. Proc Natl Acad Sci USA 2005; 102(21):7635–40.PubMedGoogle Scholar
  165. 165.
    Nusinow DA, Hernández-Muñoz I, Fazzio TG et al. Poly(ADP-ribose) polymerase 1 is inhibited by a histone H2A variant, MacroH2A and contributes to silencing of the inactive X chromosome. J Biol Chem 2007; 282(17):12851–9.PubMedGoogle Scholar
  166. 166.
    Kim MY, Zhang T, Kraus WL. Poly(ADP-ribosyl)ation by PARP-1: ‘PAR-laying’ NAD+ into a nuclear signal. Genes Dev 2005; 19(17):1951–67.PubMedGoogle Scholar
  167. 167.
    Rouleau M, Aubin RA, Poirier GG. Poly(ADP-ribosyl)ated chromatin domains: access granted. J Cell Sci 2004; 117(Pt 6):815–25.PubMedGoogle Scholar
  168. 168.
    Hassa PO, Haenni SS, Elser M et al. Nuclear ADP-ribosylation reactions in mammalian cells: where are we today and where are we going? Microbiol Mol Biol Rev 2006; 70(3):789–829.PubMedGoogle Scholar
  169. 169.
    Kim MY, Mauro S, Gévry N et al. NAD+-dependent modulation of chromatin structure and transcription by nucleosome binding properties of PARP-1. Cell 2004; 119(6):803–14.PubMedGoogle Scholar
  170. 170.
    Helbig R, Fackelmayer FO. Scaffold attachment factor A (SAF-A) is concentrated in inactive X chromosome territories through its RGG domain. Chromosoma 2003; 112(4):173–82.PubMedGoogle Scholar
  171. 171.
    Ganesan S, Silver DP, Greenberg RA et al. BRCA1 supports XIST RNA concentration on the inactive X chromosome. Cell 2002; 111(3):393–405.PubMedGoogle Scholar
  172. 172.
    Silver DP, Dimitrov SD, Feunteun J et al. Further evidence for BRCA1 communication with the inactive X chromosome. Cell 2007; 128(5):991–1002.PubMedGoogle Scholar
  173. 173.
    Vincent-Salomon A, Ganem-Elbaz C, Manié E et al. X inactive-specific transcript RNA coating and genetic instability of the X chromosome in BRCA1 breast tumors. Cancer Res 2007; 67(11):5134–40.PubMedGoogle Scholar
  174. 174.
    Xiao C, Sharp JA, Kawahara M, Davalos AR et al. The XIST noncoding RNA functions independently of BRCA1 in X inactivation. Cell 2007; 128(5):977–89.PubMedGoogle Scholar
  175. 175.
    Blewitt ME, Gendrel AV, Pang Z et al. SmcHD1, containing a structural-maintenance-of-chromosomes hinge domain, has a critical role in X inactivation. Nat Genet 2008; 40(5):663–9.PubMedGoogle Scholar
  176. 176.
    Garrick D, Sharpe JA, Arkell R et al. Loss of Atrx affects trophoblast development and the pattern of X-inactivation in extraembryonic tissues. PLoS Genet 2006; 2(4):e58.PubMedGoogle Scholar
  177. 177.
    Baumann C, De La Fuente R. ATRX marks the inactive X chromosome (Xi) in somatic cells and during imprinted X chromosome inactivation in trophoblast stem cells. Chromosoma 2009; 118(2):209–22.PubMedGoogle Scholar
  178. 178.
    Han HJ, Russo J, Kohwi Y et al. SATB1 reprogrammes gene expression to promote breast tumour growth and metastasis. Nature 2008; 452(7184):187–93.PubMedGoogle Scholar
  179. 179.
    Agrelo R, Souabni A, Novatchkova M et al. SATB1 defines the developmental context for gene silencing by Xist in lymphoma and embryonic cells. Dev Cell 2009; 16(4):507–16.PubMedGoogle Scholar
  180. 180.
    Disteche CM. Escape from X inactivation in human and mouse. Trends Genet 1995; 11(1):17–22.PubMedGoogle Scholar
  181. 181.
    Disteche CM. Escapees on the X chromosome. Proc Natl Acad Sci USA 1999; 96(25):14180–2.PubMedGoogle Scholar
  182. 182.
    Disteche CM, Filippova GN, Tsuchiya KD. Escape from X inactivation. Cytogenet Genome Res 2002; 99(1–4):36–43.PubMedGoogle Scholar
  183. 183.
    Brown CJ, Greally JM. A stain upon the silence: genes escaping X inactivation. Trends Genet 2003; 19(8):432–8.PubMedGoogle Scholar
  184. 184.
    Looijenga LH, Gillis AJ, van Gurp RJ et al. X inactivation in human testicular tumors. XIST expression and androgen receptor methylation status. Am J Pathol 1997; 151(2):581–90.PubMedGoogle Scholar
  185. 185.
    Chow JC, Hall LL, Clemson CM et al. Characterization of expression at the human XIST locus in somatic, embryonal carcinoma and transgenic cell lines. Genomics 2003; 82(3):309–22.Google Scholar
  186. 186.
    Migeon BR, Chowdhury AK, Dunston JA et al. Identification of TSIX, encoding an RNA antisense to human XIST, reveals differences from its murine counterpart: implications for X inactivation. Am J Hum Genet 2001; 69(5):951–60.PubMedGoogle Scholar
  187. 187.
    Chow JC, Hall LL, Lawrence JB et al. Ectopic XIST transcripts in human somatic cells show variable expression and localization. Cytogenet Genome Res 2002; 99(12➃):92–8.PubMedGoogle Scholar
  188. 188.
    Hall LL, Byron M, Sakai K et al. An ectopic human XIST gene can induce chromosome inactivation in postdifferentiation human HT-1080 cells. Proc Natl Acad Sci USA 2002; 99(13):8677–82.PubMedGoogle Scholar
  189. 189.
    Hall LL, Byron M, Butler J et al. X-inactivation reveals epigenetic anomalies in most hESC but identifies sublines that initiate as expected. J Cell Physiol 2008; 216(2):445–52.PubMedGoogle Scholar
  190. 190.
    Shen Y, Matsuno Y, Fouse SD et al. X-inactivation in female human embryonic stem cells is in a nonrandom pattern and prone to epigenetic alterations. Proc Natl Acad Sci USA 2008; 105(12):4709–14.PubMedGoogle Scholar
  191. 191.
    Silva SS, Rowntree RK, Mekhoubad S et al. X-chromosome inactivation and epigenetic fluidity in human embryonic stem cells. Proc Natl Acad Sci USA 2008; 105(12):4820–5.Google Scholar
  192. 192.
    Enver T, Soneji S, Joshi C et al. Cellular differentiation hierarchies in normal and culture-adapted human embryonic stem cells. Hum Mol Genet 2005; 14(21):3129–40.PubMedGoogle Scholar
  193. 193.
    Hoffman LM, Hall L, Batten JL et al. X-inactivation status varies in human embryonic stem cell lines. Stem Cells 2005; 23(10):1468–78.PubMedGoogle Scholar
  194. 194.
    Dhara SK, Benvenisty N. Gene trap as a tool for genome annotation and analysis of X chromosome inactivation in human embryonic stem cells. Nucleic Acids Res 2004; 32(13):3995–4002.PubMedGoogle Scholar
  195. 195.
    Takagi N. Imprinted X-chromosome inactivation: enlightenment from embryos in vivo. Semin Cell Dev Biol 2003; 14(6):319–29.PubMedGoogle Scholar
  196. 196.
    West JD, Papaioannou VE, Frels WI et al. Preferential expression of the maternally derived X chromosome in the mouse yolk sac. Cell 1977; 12(4):873–82.PubMedGoogle Scholar
  197. 197.
    van den Berg IM, Laven JS, Stevens M et al. X chromosome inactivation is initiated in human preimplantation embryos. Am J Hum Genet 2009; 84(6): 771-9.PubMedGoogle Scholar
  198. 198.
    Looijenga LH, Gillis AJ, Verkerk AJ et al. Heterogeneous X inactivation in trophoblastic cells of human full-term female placentas. Am J Hum Genet 1999; 64(5):1445-52.PubMedGoogle Scholar
  199. 199.
    Ropers HH, Wolff G, Hitzeroth HW. Preferential X inactivation in human placenta membranes: is the paternal X inactive in early embryonic development of female mammals? Hum Genet 1978; 43(3):265–73.PubMedGoogle Scholar
  200. 200.
    Daniels R, Zuccotti M, Kinis T et al. XIST expression in human oocytes and preimplantation embryos. Am J Hum Genet 1997; 61(1):33–9.PubMedGoogle Scholar
  201. 201.
    Ray PF, Winston RM, Handyside AH. XIST expression from the maternal X chromosome in human male preimplantation embryos at the blastocyst stage. Hum Mol Genet 1997; 6(8):1323–7.PubMedGoogle Scholar
  202. 202.
    Bamforth F, Machin G, Innes M. X-chromosome inactivation is mostly random in placental tissues of female monozygotic twins and triplets. Am J Med Genet 1996; 61(3):209–15.PubMedGoogle Scholar
  203. 203.
    Migeon BR, Wolf SF, Axelman J et al. Incomplete X chromosome dosage compensation in chorionic villi of human placenta. Proc Natl Acad Sci USA 1985; 82(10):3390–4.PubMedGoogle Scholar
  204. 204.
    Migeon BR, Axelman J, Jeppesen P. Differential X reactivation in human placental cells: implications for reversal of X inactivation. Am J Hum Genet 2005; 77(3):355–64.PubMedGoogle Scholar
  205. 205.
    Goto T, Wright E, Monk M. Paternal X-chromosome inactivation in human trophoblastic cells. Mol Hum Reprod 1997; 3(1):77–80.PubMedGoogle Scholar
  206. 206.
    Harrison KB. X-chromosome inactivation in the human cytotrophoblast. Cytogenet Cell Genet 1989; 52(1–2):37–41.PubMedGoogle Scholar
  207. 207.
    Harrison KB, Warburton D. Preferential X-chromosome activity in human female placental tissues. Cytogenet Cell Genet 1986; 41(3):163–8.PubMedGoogle Scholar
  208. 208.
    Liu W, Sun X. Skewed X chromosome inactivation in diploid and triploid female human embryonic stem cells. Hum Reprod 2009; 24(8):1834–43.PubMedGoogle Scholar
  209. 209.
    Sato N, Sanjuan IM, Heke M et al. Molecular signature of human embryonic stem cells and its comparison with the mouse. Dev Biol 2003; 260(2):404–13.PubMedGoogle Scholar
  210. 210.
    Ginis I, Luo Y, Miura T et al. Differences between human and mouse embryonic stem cells. Dev Biol 2004; 269(2):360–80.PubMedGoogle Scholar
  211. 211.
    Xu RH, Peck RM, Li DS et al. Basic FGF and suppression of BMP signaling sustain undifferentiated proliferation of human ES cells. Nat Methods 2005; 2(3):185–90.PubMedGoogle Scholar
  212. 212.
    Ying QL, Nichols J, Chambers I et al. BMP induction of Id proteins suppresses differentiation and sustains embryonic stem cell self-renewal in collaboration with STAT3. Cell 2003; 115(3):281–92.PubMedGoogle Scholar
  213. 213.
    Boyer LA, Lee TI, Cole MF et al. Core transcriptional regulatory circuitry in human embryonic stem cells. Cell 2005; 122(6):947–56.PubMedGoogle Scholar
  214. 214.
    Brons IG, Smithers LE, Trotter MW et al. Derivation of pluripotent epiblast stem cells from mammalian embryos. Nature 2007; 448(7150):191–5.PubMedGoogle Scholar
  215. 215.
    Tesar PJ, Chenoweth JG, Brook FA et al. New cell lines from mouse epiblast share defining features with human embryonic stem cells. Nature 2007; 448(7150):196–9.PubMedGoogle Scholar
  216. 216.
    Rossant J. Stem cells and early lineage development. Cell 2008; 132(4):527–31.PubMedGoogle Scholar
  217. 217.
    Lovell-Badge R. Many ways to pluripotency. Nat Biotechnol 2007; 25(10):1114–6.PubMedGoogle Scholar
  218. 218.
    Xu RH, Chen X, Li DS et al. BMP4 initiates human embryonic stem cell differentiation to trophoblast. Nat Biotechnol 2002; 20(12):1261–4.PubMedGoogle Scholar
  219. 219.
    Guo G, Yang J, Nichols J et al. Klf4 reverts developmentally programmed restriction of ground state pluripotency. Development 2009; 136(7):1063–9.PubMedGoogle Scholar
  220. 220.
    Bao S, Tang F, Li X et al. Epigenetic reversion of post-implantation epiblast to pluripotent embryonic stem cells. Nature 2009; 461(7268):1292–5.PubMedGoogle Scholar
  221. 221.
    Hanna J, Markoulaki S, Mitalipova M et al. Metastable pluripotent states in NOD-mouse-derived ESCs. Cell Stem Cell 2009; 4(6):513–24.PubMedGoogle Scholar
  222. 222.
    Nichols J, Smith A. Naive and primed pluripotent states. Cell Stem Cell 2009; 4(6):487–92.PubMedGoogle Scholar
  223. 223.
    Zvetkova I, Apedaile A, Ramsahoye B et al. Global hypomethylation of the genome in XX embryonic stem cells. Nat Genet 2005; 37(11):1274–9.Google Scholar
  224. 224.
    Lagarkova MA, Volchkov PY, Lyakisheva AV et al. Diverse epigenetic profile of novel human embryonic stem cell lines. Cell Cycle 2006; 5(4):416–20.PubMedGoogle Scholar
  225. 225.
    Rugg-Gunn PJ, Ferguson-Smith AC, Pedersen RA. Epigenetic status of human embryonic stem cells. Nat Genet 2005; 37(6):585–7.PubMedGoogle Scholar
  226. 226.
    Allegrucci C, Wu YZ, Thurston A et al. Restriction landmark genome scanning identifies culture-induced DNA methylation instability in the human embryonic stem cell epigenome. Hum Mol Genet 2007; 16(10):1253–68.PubMedGoogle Scholar

Copyright information

© Landes Bioscience and Springer Science+Business Media 2010

Authors and Affiliations

  1. 1.Department of Reproduction and DevelopmentUniversity Medical CenterRotterdamNetherlands

Personalised recommendations