Retinoic acid accelerates downregulation of the Xist repressor, Oct4, and increases the likelihood of Xist activation when Tsix is deficient

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• 作者：Janice Y Ahn (1) (2)
  Jeannie T Lee (1)
  
• 刊名：BMC Developmental Biology
• 出版年：2010
• 出版时间：December 2010
• 年：2010
• 卷：10
• 期：1
• 全文大小：1652KB
• 参考文献：1. Lyon MF: Gene action in the X-chromosome of the mouse (Mus musculus L.). / Nature 1961, 190:372鈥?73. CrossRef
  2. Payer B, Lee JT: X chromosome dosage compensation: how mammals keep the balance. / Annu Rev Genet 2008, 42:733鈥?72. CrossRef
  3. Avner P, Heard E: X-chromosome inactivation: counting, choice and initiation. / Nat Rev Genet 2001, 2:59鈥?7. CrossRef
  4. Lucchesi JC, Kelly WG, Panning B: Chromatin remodeling in dosage compensation. / Annu Rev Genet 2005, 39:615鈥?51. CrossRef
  5. Wutz A, Gribnau J: X inactivation Xplained. / Curr Opin Genet Dev 2007, 17:387鈥?93. CrossRef
  6. Clemson CM, McNeil JA, Willard HF, Lawrence JB: XIST RNA paints the inactive X chromosome at interphase: evidence for a novel RNA involved in nuclear/chromosome structure. / J Cell Biol 1996, 132:259鈥?75. CrossRef
  7. Penny GD, Kay GF, Sheardown SA, Rastan S, Brockdorff N: Requirement for Xist in X chromosome inactivation. / Nature 1996, 379:131鈥?37. CrossRef
  8. Zhao J, Sun BK, Erwin JA, Song JJ, Lee JT: Polycomb proteins targeted by a short repeat RNA to the mouse X chromosome. / Science 2008, 322:750鈥?56. CrossRef
  9. Plath K, Fang J, Mlynarczyk-Evans SK, Cao R, Worringer KA, Wang H, de la Cruz CC, Otte AP, Panning B, Zhang Y: Role of histone H3 lysine 27 methylation in X inactivation. / Science 2003, 300:131鈥?35. CrossRef
  10. Silva J, Mak W, Zvetkova I, Appanah R, Nesterova TB, Webster Z, Peters AH, Jenuwein T, Otte AP, Brockdorff N: Establishment of histone h3 methylation on the inactive X chromosome requires transient recruitment of Eed-Enx1 polycomb group complexes. / Dev Cell 2003, 4:481鈥?95. CrossRef
  11. Martin GR, Epstein CJ, Travis B, Tucker G, Yatziv S, Martin DW Jr, Clift S, S C: X-chromosome inactivation during differentiation of female teratocarcinoma stem cells in vitro. / Nature 1978, 271:329鈥?33. CrossRef
  12. Rastan S, Robertson E: X chromosome deletions in embryo-derived (EK) cell lines associated with the lack of X chromosome inactivation. / J Embryol Exp Morphol 1985, 90:379鈥?88.
  13. Lee JT, Lu N: Targeted mutagenesis of Tsix leads to nonrandom X inactivation. / Cell 1999, 99:47鈥?7. CrossRef
  14. Sado T, Wang Z, Sasaki H, Li E: Regulation of imprinted X-chromosome inactivation in mice by Tsix. / Development 2001, 128:1275鈥?286.
  15. Lee JT: Regulation of X-chromosome counting by Tsix and Xite sequences. / Science 2005, 309:768鈥?71. CrossRef
  16. Xu N, Tsai CL, Lee JT: Transient homologous chromosome pairing marks the onset of X inactivation. / Science 2006, 311:1149鈥?152. CrossRef
  17. Bacher CP, Guggiari M, Brors B, Augui S, Clerc P, Avner P, Eils R, Heard E: Transient colocalization of X-inactivation centres accompanies the initiation of X inactivation. / Nat Cell Biol 2006, 8:293鈥?99. CrossRef
  18. Ogawa Y, Lee JT: Xite, X-inactivation intergenic transcription elements that regulate the probability of choice. / Mol Cell 2003, 11:731鈥?43. CrossRef
  19. Vigneau S, Augui S, Navarro P, Avner P, Clerc P: 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, 103:7390鈥?395. CrossRef
  20. Luikenhuis S, Wutz A, Jaenisch R: Antisense transcription through the Xist locus mediates Tsix function in embryonic stem cells. / Mol Cell Biol 2001, 21:8512鈥?520. CrossRef
  21. Clerc P, Avner P: Role of the region 3' to Xist exon 6 in the counting process of X-chromosome inactivation. / Nat Genet 1998, 19:249鈥?53. CrossRef
  22. Morey C, Navarro P, Debrand E, Avner P, Rougeulle C, Clerc P: The region 3' to Xist mediates X chromosome counting and H3 Lys-4 dimethylation within the Xist gene. / Embo J 2004, 23:594鈥?04. CrossRef
  23. Monkhorst K, Jonkers I, Rentmeester E, Grosveld F, Gribnau J: X inactivation counting and choice is a stochastic process: evidence for involvement of an X-linked activator. / Cell 2008, 132:410鈥?21. CrossRef
  24. Sado T, Li E, Sasaki H: Effect of TSIX disruption on XIST expression in male ES cells. / Cytogenet Genome Res 2002, 99:115鈥?18. CrossRef
  25. Navarro P, Chambers I, Karwacki-Neisius V, Chureau C, Morey C, Rougeulle C, Avner P: Molecular coupling of Xist regulation and pluripotency. / Science 2008, 321:1693鈥?695. CrossRef
  26. Donohoe ME, Silva SS, Pinter SF, Xu N, Lee JT: The pluripotency factor Oct4 interacts with Ctcf and also controls X-chromosome pairing and counting. / Nature 2009, 460:128鈥?32. CrossRef
  27. Scholer HR, Balling R, Hatzopoulos AK, Suzuki N, Gruss P: Octamer binding proteins confer transcriptional activity in early mouse embryogenesis. / Embo J 1989, 8:2551鈥?557.
  28. Okamoto K, Okazawa H, Okuda A, Sakai M, Muramatsu M, Hamada H: A novel octamer binding transcription factor is differentially expressed in mouse embryonic cells. / Cell 1990, 60:461鈥?72. CrossRef
  29. Rosner MH, Vigano MA, Ozato K, Timmons PM, Poirier F, Rigby PW, Staudt LM: A POU-domain transcription factor in early stem cells and germ cells of the mammalian embryo. / Nature 1990, 345:686鈥?92. CrossRef
  30. Schoorlemmer J, Kruijer W: Octamer-dependent regulation of the kFGF gene in embryonal carcinoma and embryonic stem cells. / Mech Dev 1991, 36:75鈥?6. CrossRef
  31. Allenby G, Bocquel MT, Saunders M, Kazmer S, Speck J, Rosenberger M, Lovey A, Kastner P, Grippo JF, Chambon P, / et al.: Retinoic acid receptors and retinoid X receptors: interactions with endogenous retinoic acids. / Proc Natl Acad Sci USA 1993, 90:30鈥?4. CrossRef
  32. Morey C, Arnaud D, Avner P, Clerc P: Tsix-mediated repression of Xist accumulation is not sufficient for normal random X inactivation. / Hum Mol Genet 2001, 10:1403鈥?411. CrossRef
  33. Sheardown SA, Duthie SM, Johnston CM, Newall AE, Formstone EJ, Arkell RM, Nesterova TB, Alghisi GC, Rastan S, Brockdorff N: Stabilization of Xist RNA mediates initiation of X chromosome inactivation. / Cell 1997, 91:99鈥?07. CrossRef
  34. Stavropoulos N, Lu N, Lee JT: A functional role for Tsix transcription in blocking Xist RNA accumulation but not in X-chromosome choice. / Proc Natl Acad Sci USA 2001, 98:10232鈥?0237. CrossRef
  35. Ovitt CE, Scholer HR: The molecular biology of Oct-4 in the early mouse embryo. / Mol Hum Reprod 1998, 4:1021鈥?031. CrossRef
  36. Namekawa SH, Payer B, Huynh KD, Jaenisch R, Lee JT: Two-step imprinted X-inactivation: Repeat vs genic silencing in the mouse. / Mol Cell Biol
  37. Clemson CM, Hall LL, Byron M, McNeil J, Lawrence JB: 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, 103:7688鈥?693. CrossRef
  38. Hall LL, Byron M, Sakai K, Carrel L, Willard HF, Lawrence JB: An ectopic human XIST gene can induce chromosome inactivation in postdifferentiation human HT-1080 cells. / Proc Natl Acad Sci USA 2002, 99:8677鈥?682. CrossRef
  39. Huynh KD, Lee JT: Inheritance of a pre-inactivated paternal X chromosome in early mouse embryos. / Nature 2003, 426:857鈥?62. CrossRef
  40. Kastner P, Perez A, Lutz Y, Rochette-Egly C, Gaub MP, Durand B, Lanotte M, Berger R, Chambon P: Structure, localization and transcriptional properties of two classes of retinoic acid receptor alpha fusion proteins in acute promyelocytic leukemia (APL): structural similarities with a new family of oncoproteins. / Embo J 1992, 11:629鈥?42.
  41. Chambon P: The molecular and genetic dissection of the retinoid signalling pathway. / Gene 1993, 135:223鈥?28. CrossRef
  42. Heyman RA, Mangelsdorf DJ, Dyck JA, Stein RB, Eichele G, Evans RM, Thaller C: 9-cis retinoic acid is a high affinity ligand for the retinoid X receptor. / Cell 1992, 68:397鈥?06. CrossRef
  43. Levin AA, Sturzenbecker LJ, Kazmer S, Bosakowski T, Huselton C, Allenby G, Speck J, Kratzeisen C, Rosenberger M, Lovey A, / et al.: 9-cis retinoic acid stereoisomer binds and activates the nuclear receptor RXR alpha. / Nature 1992, 355:359鈥?61. CrossRef
  44. Mangelsdorf DJ, Borgmeyer U, Heyman RA, Zhou JY, Ong ES, Oro AE, Kakizuka A, Evans RM: Characterization of three RXR genes that mediate the action of 9-cis retinoic acid. / Genes Dev 1992, 6:329鈥?44. CrossRef
  45. Yu VC, Delsert C, Andersen B, Holloway JM, Devary OV, Naar AM, Kim SY, Boutin JM, Glass CK, Rosenfeld MG: RXR beta: a coregulator that enhances binding of retinoic acid, thyroid hormone, and vitamin D receptors to their cognate response elements. / Cell 1991, 67:1251鈥?266. CrossRef
  46. Bugge TH, Pohl J, Lonnoy O, Stunnenberg HG: RXR alpha, a promiscuous partner of retinoic acid and thyroid hormone receptors. / Embo J 1992, 11:1409鈥?418.
  47. Kliewer SA, Umesono K, Heyman RA, Mangelsdorf DJ, Dyck JA, Evans RM: Retinoid X receptor-COUP-TF interactions modulate retinoic acid signaling. / Proc Natl Acad Sci USA 1992, 89:1448鈥?452. CrossRef
  48. Leid M, Kastner P, Lyons R, Nakshatri H, Saunders M, Zacharewski T, Chen JY, Staub A, Garnier JM, Mader S, / et al.: Purification, cloning, and RXR identity of the HeLa cell factor with which RAR or TR heterodimerizes to bind target sequences efficiently. / Cell 1992, 68:377鈥?95. CrossRef
  49. Marks MS, Hallenbeck PL, Nagata T, Segars JH, Appella E, Nikodem VM, Ozato K: H-2RIIBP (RXR beta) heterodimerization provides a mechanism for combinatorial diversity in the regulation of retinoic acid and thyroid hormone responsive genes. / Embo J 1992, 11:1419鈥?435.
  50. Pikarsky E, Sharir H, Ben-Shushan E, Bergman Y: Retinoic acid represses Oct-3/4 gene expression through several retinoic acid-responsive elements located in the promoter-enhancer region. / Mol Cell Biol 1994, 14:1026鈥?038.
  51. Schoorlemmer J, van Puijenbroek A, van Den Eijnden M, Jonk L, Pals C, Kruijer W: Characterization of a negative retinoic acid response element in the murine Oct4 promoter. / Mol Cell Biol 1994, 14:1122鈥?136.
  52. Gu P, LeMenuet D, Chung AC, Mancini M, Wheeler DA, Cooney AJ: Orphan nuclear receptor GCNF is required for the repression of pluripotency genes during retinoic acid-induced embryonic stem cell differentiation. / Mol Cell Biol 2005, 25:8507鈥?519. CrossRef
  53. Marin M, Karis A, Visser P, Grosveld F, Philipsen S: Transcription factor Sp1 is essential for early embryonic development but dispensable for cell growth and differentiation. / Cell 1997, 89:619鈥?28. CrossRef
  54. Sylvester I, Scholer HR: Regulation of the Oct-4 gene by nuclear receptors. / Nucleic Acids Res 1994, 22:901鈥?11. CrossRef
  55. Sun BK, Deaton AM, Lee JT: A transient heterochromatic state in Xist preempts X inactivation choice without RNA stabilization. / Mol Cell 2006, 21:617鈥?28. CrossRef
  56. Buzin CH, Mann JR, Singer-Sam J: Quantitative RT-PCR assays show Xist RNA levels are low in mouse female adult tissue, embryos and embryoid bodies. / Development 1994, 120:3529鈥?536.
  57. Panning B, Dausman J, Jaenisch R: X chromosome inactivation is mediated by Xist RNA stabilization. / Cell 1997, 90:907鈥?16. CrossRef
  58. Navarro P, Pichard S, Ciaudo C, Avner P, Rougeulle C: Tsix transcription across the Xist gene alters chromatin conformation without affecting Xist transcription: implications for X-chromosome inactivation. / Genes Dev 2005, 19:1474鈥?484. CrossRef
  59. Ogawa Y, Sun BK, Lee JT: Intersection of the RNA interference and X-inactivation pathways. / Science 2008, 320:1336鈥?341. CrossRef
  60. Wutz A, Jaenisch R: A shift from reversible to irreversible X inactivation is triggered during ES cell differentiation. / Mol Cell 2000, 5:695鈥?05. CrossRef
  61. Sado T, Hoki Y, Sasaki H: Tsix silences Xist through modification of chromatin structure. / Dev Cell 2005, 9:159鈥?65. CrossRef
  62. Minucci S, Botquin V, Yeom YI, Dey A, Sylvester I, Zand DJ, Ohbo K, Ozato K, Scholer HR: Retinoic acid-mediated down-regulation of Oct3/4 coincides with the loss of promoter occupancy in vivo. / Embo J 1996, 15:888鈥?99.
  63. Monkhorst K, de Hoon B, Jonkers I, Mulugeta Achame E, Monkhorst W, Hoogerbrugge J, Rentmeester E, Westerhoff HV, Grosveld F, Grootegoed JA, Gribnau J: 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:e5616. CrossRef
  64. Starmer J, Magnuson T: A new model for random X chromosome inactivation. / Development 2009, 136:1鈥?0. CrossRef
  65. Jonkers I, Barakat TS, Achame EM, Monkhorst K, Kenter A, Rentmeester E, Grosveld F, Grootegoed JA, Gribnau J: RNF12 is an X-Encoded dose-dependent activator of X chromosome inactivation. / Cell 2009, 139:999鈥?011. CrossRef
  66. Lee JT: Disruption of imprinted X inactivation by parent-of-origin effects at Tsix. / Cell 2000, 103:17鈥?7. CrossRef
  67. Panning B, Jaenisch R: DNA hypomethylation can activate Xist expression and silence X-linked genes. / Genes Dev 1996, 10:1991鈥?002. CrossRef
  68. Livak KJ, Schmittgen TD: Analysis of relative gene expression data using real-time quantitative PCR and the 2(-Delta Delta C(T)) Method. / Methods 2001, 25:402鈥?08. CrossRef
  
• 作者单位：Janice Y Ahn (1) (2)
  Jeannie T Lee (1)
  
  1. Howard Hughes Medical Institute Department of Molecular Biology, Massachusetts General Hospital Department of Genetics, Harvard Medical School Boston, MA, 02114, USA
  2. Department of Molecular and Cellular Biology, Harvard University Cambridge, MA, 02138, USA
  

文摘

Background Imbalances in X-linked gene dosage between the sexes are resolved by transcriptionally silencing one of two X-chromosomes in female cells of the early mammalian embryo. X-inactivation is triggered by expression of the non-coding Xist gene. In turn, Xist is dually regulated by the antisense Tsix RNA and by the Oct4 pluripotency factor. Although there is general agreement that Tsix is an inhibitor of Xist, some laboratories have observed ectopic Xist induction in differentiating male ES cells when Tsix is mutated, whereas we have not observed significant changes in Xist. These observational differences have led to fundamentally diverse models of X-chromosome counting. Here, we investigate if different methods of cell differentiation and use of all -trans retinoic acid (RA) could be causative factors and how they might impact Xist expression. Results We compared suspension and cell-adhesion cultures in the presence or absence of RA and find that RA significantly impacts Xist expression in Tsix-mutant male cells. Whereas the standard embryoid body method infrequently leads to ectopic Xist expression, adding RA generates a significant number of Xist-positive male cells. However, while normal Xist clouds in wild-type female cells are robust and well-circumscribed, those found in the RA-treated mutant males are loosely dispersed. Furthermore, ectopic Xist expression does not generally lead to complete gene silencing. We attribute the effect of RA on Xist to RA's repressive influence on Oct4, a pluripotency factor recently shown to regulate Tsix and Xist. RA-treated ES cells exhibit accelerated decreases in Oct4 RNA levels and also display accelerated loss of binding to Xist intron 1. When Tsix is deficient, the faster kinetics of Oct4 loss tip the equilibrium towards Xist expression. However, the aberrant Xist clusters are unlikely to explain elevated cell death, as X-linked silencing does not necessarily correlate with the qualitatively aberrant Xist clusters. Conclusions We conclude that RA treatment leads to premature downregulation of Oct4 and partial derepression of Xist irrespective of X-chromosome counting. RA-induced Xist clusters in male cells do not result in global or stable silencing, and excess cell death is not observed. These data and RA's known pleiotropic effects on ES transcription networks suggest that RA differentation bypasses normal X-inactivation controls and should be used judiciously. We propose that the likelihood of Xist expression is determined by a balance of multiple Xist activators and repressors, and that levels of Oct4 and Tsix are crucial toward achieving this balance.