The role of Xist in X-inactivation

Current Opinion in Genetics and Development

Volumn 8, Issue 3, 1998, Pages 328-333

  Brockdorff, Neil ^a  

^a IMPERIAL COLLEGE SCHOOL OF MEDICINE   (United Kingdom)

Author keywords

[No Author keywords available]

Indexed keywords

RNA;

GENE EXPRESSION REGULATION; HUMAN; MOLECULAR STABILITY; MOUSE; NONHUMAN; PRIORITY JOURNAL; REVIEW; TRANSGENE; X CHROMOSOME;

EID: 0032102617     PISSN: 0959437X     EISSN: None     Source Type: Journal    
DOI: 10.1016/S0959-437X(98)80090-7     Document Type: Article

References (45)

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2. Rastan S. X chromosome inactivation and the Xist gene. Curr Opin Genet Dev. 4:1994;292-297.
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8. Brockdorff N, Ashworth A, Kay GF, Cooper PJ, Smith S, McCabe VM, Norris DP, Penny GD, Patel D, Rastan S. Conservation of position and exclusive expression of mouse Xist from the inactive X chromosome. Nature. 351:1991;329-331.
9. Borsani G, Tonlorenzi R, Simmler MC, Dandolo L, Arnaud D, Capra V, Grompe M, Pizzuti A, Muzny D, Lawrence C, et al. Characterisation of a murine gene expressed from the inactive X chromosome. Nature. 351:1991;325-329.
10. Brown CJ, Hendrich BD, Rupert JL, Lafreniere RG, Xing Y, Lawrence J, Willard HF. The human Xist gene: analysis of a 17 kb inactive X specific RNA that contains conserved repeats and is highly localised within the nucleus. Cell. 71:1992;527-542.
11. Brockdorff N, Ashworth A, Kay GF, McCabe VM, Norris DP, Cooper PJ, Swift S, Rastan S. The product of the mouse Xist gene is a 15kb inactive X-specific transcript containing no conserved ORF and located exclusively in the nucleus. Cell. 71:1992;515-526.
12. Simmler MC, Cattanach BM, Rasberry C, Rougeulle C, Avner P. Mapping the murine Xce locus with (CA)n repeats. Mamm Genome. 4:1993;523-530.
13. Penny GD, Kay GF, Sheardown SA, Rastan S, Brockdorff N. Requirement for Xist in X chromosome inactivation. Nature. 379:1996;131-137.
14. Lee JT, Strauss WM, Dausman JA, Jaenisch R. A 450 Kb transgene displays properties of the mammalian X inactivation center. Cell. 86:1996;83-94.
15. Lee JT, Jaenisch R. Long range cis effects of ectopic X inactivation centres on a mouse autosome. of outstanding interest Nature. 386:1997;275-279 This paper shows that a multicopy Xist transgene integrated into mouse chromosome 12 causes cis-repression of autosomal genes that are up to 50 cM distant. In addition, the autosome adopts cytogenetic features characteristic of the inactive X chromosome (i.e. replication late in S-phase and underacetylation of histone H4).
16. Heard E, Kress C, Mongelard F, Courtier B, Rougeulle C, Ashworth A, Vourch C, Babinet C, Avner P. Transgenic mice carrying an Xist-containing YAC. Hum Mol Genet. 5:1996;441-450.
17. Matsuura S, Episkopou V, Hamvas R, Brown SDM. Xist expression from an Xist YAC transgene carried on the mouse Y chromosome. Hum Mol Genet. 5:1996;451-459.
18. Herzing LBK, Romer JT, Horn JM, Ashworth A. Xist has properties of the X chromosome inactivation centre. of outstanding interest Nature. 386:1997;272-275 A demonstration that a cosmid construct encompassing the Xist locus can recapitulate functions of the Xic when integrated into an ectopic site in XY ES cells. Previous studies demonstrated that the entire Xic must lie within ≈400 kb spanning Xist. This result therefore considerably narrows the critical Xic region.
19. Horn JM, Ashworth A. A member of the caudal family of homeobox genes maps to the X-inactivation centre region of the mouse and human X chromosomes. Hum Mol Genet. 4:1995;1041-1047.
20. Simmler MC, Cunningham DB, Clerc P, Vermat T, Caudron B, Cruaud C, Pawlak A, Szpirer C, Weissenbach J, Claverie JM, Avner P. 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. 5:1996;1713-1726.
21. Rougeulle C, Avner P. Cloning and characterization of a murine brain specific gene Bpx and its human homologue lying within the Xic candidate region. Hum Mol Genet. 5:1996;41-49.
22. Simmler MC, Heard E, Rougeulle C, Cruaud C, Weissenbach J, Avner P. Localization and expression analysis of a novel conserved brain expressed transcript, Brx/BRX, lying within the Xic/XIC candidate region. of special interest Mamm Genome. 8:1997;760-766 The latest in a series of papers [19-21,22] describing genes located in the critical Xic region. Taken together, these papers support the notion that the Xist gene is in itself the Xic. Additionally, mapping these genes in mouse and human has helped to define an evolutionary inversion of the Xic region that encompasses ≈600kb.
23. Marahrens Y, Panning B, Dausman J, Strauss W, Jaenisch R. Xist deficient mice are defective in dosage compensation but not spermatogenesis. of outstanding interest Genes Dev. 11:1997;156-166 Gene targeting was used to introduce a large deletion in the transcribed region of the mouse Xist gene in XY ES cells. Male chimaeras transmitted the mutation, demonstrating that Xist is not required for spermatogenesis. The mutation causes early lethality in XX progeny when transmitted through the male but not the female germline (XX progeny survive but show complete non-random X-inactivation of the X chromosome bearing the normal allele). Lethality on paternal transmission is shown to be caused by failure of imprinted X-inactivation.
24. Plenge RM, Hendrich BD, Schwartz C, Arena JF, Naumova A, Sapienza C, Winter RM, Willard HF. A promoter mutation in the Xist gene in two unrelated families with skewed x chromosome inactivation. of outstanding interest Nat Genet. 17:1997;353-356 Description of a point mutation in the minimal promoter region of the human Xist gene which occurs in two independent kindreds displaying non-random, or skewed X-inactivation. All females show preferential inactivation of the X chromosome carrying the mutation. In vitro reporter assays demonstrate that the mutant promoter has reduced activity (two- to five-fold) compared to the wild-type.
25. Panning B, Dausman J, Jaenisch R. X Chromosome inactivation is mediated by Xist RNA stabilization. of outstanding interest Cell. 90:1997;907-916 This paper demonstrates that upregulation of Xist RNA at the onset of random X-inactivation in mouse embryos is attributable to increased stability of the transcript. Transcription rates of Xist are shown to be similar in XY ES cells and in somatic cells. In addition, it is shown that the Xist allele on the active X chromosome continues to transcribe unstable transcript for a considerable time after stabilisation and cis-accumulation of the inactive X allele.
26. Sheardown SA, Duthie SM, Johnston CM, Newall AET, Formstone EJ, Arkell RM, Nesterova TB, Alghisi GC, Rastan S, Brockdorff N. Stabilization of Xist RNA mediates initiation of X chromosome inactivation. of outstanding interest Cell. 91:1997;99-107 This paper reports similar findings to the previous paper [25]. Additionally, quantitative analysis indicates that upregulation of steady-state levels may be solely attributable to transcript stabilisation. Progression through the different steps is shown for XX ES cells differentiated in vitro as well as in embryos undergoing random X-inactivation. Finally, this paper demonstrates that all cells of early preimplantation XX embryos exhibit stable accumulated transcript from the paternal X chromosome. Significantly, both X chromosomes are active at these stages.
27. Hendrich BD, Plenge RM, Willard HF. Identification and characterization of the human Xist gene promoter: implications for models of X chromosome inactivation. of special interest Nucleic Acids Res. 25:1997;2661-2671 A detailed analysis of the minimal promoter region of the human Xist gene, identifying binding sites for TFIID, CBP and SP1. In vitro assays demonstrate that the promoter is constitutively active in somatic cells. Additionally, this study describes a putative upstream regulatory element that represses the minimal promoter in in vitro assays, and a downstream element that increases activity of the minimal promoter.
28. Sheardown SA, Newall AET, Norris DP, Rastan S, Brockdorff N. Regulatory elements in the minimal promoter region of the mouse Xist gene. of special interest Gene. 203:1997;159-168 A detailed analysis of the minimal promoter region of the mouse Xist gene. Findings are similar to those for the human gene in the previous reference [27]. The mouse promoter is shown to be constitutively active in ES cells both before and after differentiation in vitro.
29. Komura J, Sheardown SA, Brockdorff N, Singersam J, Riggs AD. In vivo ultraviolet and dimethyl sulfate footprinting of the 5′ region of the expressed and silent Xist alleles. of special interest J Biol Chem. 272:1997;10975-10980 In vivo footprinting is used to demonstrate occupation of the TFIID, CBP and SP1 sites on the expressed allele of the mouse minimal promoter. This provides a first insight into the transcription factors which may be involved in regulating the initiation of X-inactivation in vivo.
30. Panning B, Jaenisch R. DNA hypomethylation can activate Xist expression and silence X-linked genes. Genes Dev. 10:1996;1991-2002.
31. 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. 132:1996;259-275.
32. Beard C, Li E, Jaenisch R. Loss of methylation activates Xist in somatic but not in embryonic cells. Genes Dev. 9:1995;2325-2334.
33. Brown CJ, Baldry SEL. Evidence that heteronuclear proteins interact with the Xist RNA in vitro. of special interest Somat Cell Mol Genet. 22:1996;403-417 The authors of this paper describe the identification of two 40 kDa RNA binding proteins that interact strongly with a conserved region at the 5′ end of the Xist transcript. Preliminary characterisation indicates that these proteins may be hnRNPC1/C2.
34. Kay GF, Penny GD, Patel D, Ashworth A, Brockdorff N, Rastan S. Expression of Xist during mouse development suggests a role in the initiation of X chromosome inactivation. Cell. 72:1993;171-182.
35. Yoshida I, Nishita Y, Mohandas TK, Takagi N. Reactivation of an inactive human x chromosome introduced into mouse embryonal carcinoma cells by microcell fusion with persistent expression of Xist. of special interest Exp Cell Res. 230:1997;208-219 Fusions between some embryonal carcinoma (EC) cell lines and XX somatic cells results in reactivation of the somatic cell derived inactive X chromosome. This is thought to result from dominance of the EC cell phenotype. In this paper, it is shown that fusions between mouse EC cells and human XX somatic cells reactivate the human inactive X chromosome. Human Xist RNA is transcribed at a similar level in fusions and the parent cell line, indicating that the presence of Xist RNA is not sufficient to cause X-inactivation under these circumstances.
36. Ray PF, Winston RML, Handyside AH. Xist Expression from the maternal X chromosome in human male preimplantation embryos at the blastocyst stage. of special interest Hum Mol Genet. 6:1997;1323-1327 This study is an analysis of Xist expression in human preimplantation embryos using RT-PCR. As is the case for mouse XX embryos, transcripts were detected at a very early stage (5-10 cells onwards). In contrast to mouse, however, expression was also detected in XY embryos (i.e. from the maternal X chromosome). These findings suggest that Xist expression (and hence X-inactivation?) in early human embryos is not subject to a genomic imprinting effect.
37. Daniels R, Zuccotti M, Kinis T, Serhal P, Monk M. Xist expression in human oocytes and preimplantation embryos. of special interest Am J Hum Genet. 61:1997;33-39 Similar results to those reported in the previous paper [36] were obtained. In addition, it was shown that Xist expression can be detected as early as the one-cell stage in human embryos.
38. Norris DP, Patel D, Kay GF, Penny GD, Brockdorff N, Sheardown SA, Rastan S. Evidence that random and imprinted Xist expression is controlled by preemptive methylation. Cell. 77:1994;41-51.
39. Ariel M, Robinson E, McCarrey JR, Cedar H. Gamete-specific methylation correlates with imprinting of the murine Xist gene. Nat Genet. 9:1995;312-315.
40. Zuccotti M, Monk M. Methylation of the mouse Xist gene in sperm and eggs correlates with imprinted Xist expression and paternal X-inactivation. Nat Genet. 9:1995;316-332.
41. Huntriss J, Lorenzi R, Purewal A, Monk M. A methylation dependent DNA binding activity recognising the methylated promoter region of the mouse Xist gene. of special interest Biochem Biophys Res Commun. 235:1997;730-738 The authors methylation-dependent binding activity that interacts with the Xist minimal promoter in an in vitro binding assay. It is suggested that this 100 kDa factor, which is present in all nuclear extracts tested, may play a role in the regulation of both imprinted and random X-inactivation.
42. McCarrey JR, Dilworth DD. Expression of Xist in mouse germ cells correlates with X-chromosome inactivation. Nat Genet. 2:1992;200-203.
43. Salido EC, Yen PH, Mohandas TK, Shapiro LJ. Expression of the X inactivation-associated gene Xist during spermatogenesis. Nat Genet. 2:1992;196-199.
44. Richler C, Soreq H, Wahrman J. X inactivation in mammalian testis is correlated with inactive X-specific transcription. Nat Genet. 2:1992;192-195.
45. Ayoub N, Richler C, Wahrman J. Xist RNA is associated with the transcriptionally inactive XY body in mammalian male meiosis. of special interest Chromosoma. 106:1997;1-10 This paper utilizes in situ RT-PCR detection to analyse the localisation of Xist RNA in adult male germ cells. A signal was detected in the XY body of primary spermatocytes and it appeared to coat both the X and Y chromosome components of the XY bivalent in pachytene spermatocytes.