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Gene Review

Xist  -  inactive X specific transcripts

Mus musculus

Synonyms: A430022B11, AI314753
 
 
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Disease relevance of Xist

 

High impact information on Xist

  • Tsix controls X-chromosome inactivation (XCI) by blocking the accumulation of Xist RNA on the future active X chromosome [3].
  • The gene Xist initiates the chromosomal silencing process of X inactivation in mammals [4].
  • Deletion of this element results in Xist RNA that still associates with chromatin and spreads over the chromosome but does not effect transcriptional repression [4].
  • We found aberrant expression patterns in nine of ten X-linked genes and hypomethylation of Xist in organs of deceased clones [5].
  • Here we use an inducible Xist expression system in mouse embryonic stem cells that recapitulates long-range chromosomal silencing to elucidate which Xist RNA sequences are necessary for chromosomal association and silencing [4].
 

Biological context of Xist

  • Expression of Xist during mouse development suggests a role in the initiation of X chromosome inactivation [6].
  • Our data support a direct role for Xist in the initiation of X inactivation [6].
  • This phenotype is similar to that seen with mutations that ablate Tsix, an antisense RNA initiated 3' of Xist [7].
  • Xce haplotypes show modified methylation in a region of the active X chromosome lying 3' to Xist [8].
  • One such element, lying 15 kb downstream of Xist, is the DXPas34 locus, which was first identified as a result of its hypermethylation on the active X chromosome and the correlation of its methylation level with allelism at the X-controlling element (Xce), a locus known to affect choice [9].
 

Anatomical context of Xist

  • The earliest Xist expression in morulae and blastocysts is imprinted, resulting in specific expression of the paternal Xist allele [6].
  • In addition, we found that the allelic ratio of Xist transcripts from reciprocal (XX) ES cell lines differentiating in vitro was identical to that of isogenic 10.5 to 11.5 day female embryos [10].
  • The Xist RNA was expressed at a greater abundance in androgenones than in gynogenones at the eight-cell and morula stages, consistent with previous studies [11].
  • The creation of a null allele of Xist in embryonic stem cells has demonstrated that this gene is required for X inactivation to occur in cis [12].
  • A 94 kb genomic sequence 3' to the murine Xist gene reveals an AT rich region containing a new testis specific gene Tsx [13].
 

Associations of Xist with chemical compounds

 

Physical interactions of Xist

 

Regulatory relationships of Xist

  • X chromosome choice is determined by asymmetric expression of Tsix whose antisense action represses Xist [21].
  • Analysis of F1 heterozygous female mice from T(X;16)16H x MSM crosses and two cell clones derived from inter-subspecific F1 female mice demonstrated that the packaging level of the transcribed Xist region on inactive X Chr was as tight as that of the repressed Pgk-1 allele on the same chromosome [22].
  • We show that Xist expression is appropriately regulated in the absence of Dnmt3a and Dnmt3b and that a single X chromosome undergoes proper inactivation in mutant females [23].
  • Only the paternal Xist is expressed in preimplantation development beginning from the 4-cell stage, preceding and in correlation with paternal X-inactivation in the extraembryonic lineage of the blastocyst [24].
  • By using an allele-specific general DNaseI sensitivity assay we show that there is preferential digestion of the expressed allele at sites within the transcribed locus but not in flanking sites located up to 70 kb 5'. A putative proximal boundary for the Xist domain is located within 10 kb upstream of promoter P1 [25].
 

Other interactions of Xist

 

Analytical, diagnostic and therapeutic context of Xist

References

  1. Praja1, a novel gene encoding a RING-H2 motif in mouse development. Mishra, L., Tully, R.E., Monga, S.P., Yu, P., Cai, T., Makalowski, W., Mezey, E., Pavan, W.J., Mishra, B. Oncogene (1997) [Pubmed]
  2. Xist is expressed in female embryonal carcinoma cells with two active X chromosomes. Tai, H.H., Gordon, J., McBurney, M.W. Somat. Cell Mol. Genet. (1994) [Pubmed]
  3. Homozygous Tsix mutant mice reveal a sex-ratio distortion and revert to random X-inactivation. Lee, J.T. Nat. Genet. (2002) [Pubmed]
  4. Chromosomal silencing and localization are mediated by different domains of Xist RNA. Wutz, A., Rasmussen, T.P., Jaenisch, R. Nat. Genet. (2002) [Pubmed]
  5. Aberrant patterns of X chromosome inactivation in bovine clones. Xue, F., Tian, X.C., Du, F., Kubota, C., Taneja, M., Dinnyes, A., Dai, Y., Levine, H., Pereira, L.V., Yang, X. Nat. Genet. (2002) [Pubmed]
  6. Expression of Xist during mouse development suggests a role in the initiation of X chromosome inactivation. Kay, G.F., Penny, G.D., Patel, D., Ashworth, A., Brockdorff, N., Rastan, S. Cell (1993) [Pubmed]
  7. Skewing X chromosome choice by modulating sense transcription across the Xist locus. Nesterova, T.B., Johnston, C.M., Appanah, R., Newall, A.E., Godwin, J., Alexiou, M., Brockdorff, N. Genes Dev. (2003) [Pubmed]
  8. Xce haplotypes show modified methylation in a region of the active X chromosome lying 3' to Xist. Courtier, B., Heard, E., Avner, P. Proc. Natl. Acad. Sci. U.S.A. (1995) [Pubmed]
  9. Functional analysis of the DXPas34 locus, a 3' regulator of Xist expression. Debrand, E., Chureau, C., Arnaud, D., Avner, P., Heard, E. Mol. Cell. Biol. (1999) [Pubmed]
  10. Quantitative RT-PCR assays show Xist RNA levels are low in mouse female adult tissue, embryos and embryoid bodies. Buzin, C.H., Mann, J.R., Singer-Sam, J. Development (1994) [Pubmed]
  11. Expression of X-linked genes in androgenetic, gynogenetic, and normal mouse preimplantation embryos. Latham, K.E., Rambhatla, L. Dev. Genet. (1995) [Pubmed]
  12. Xist has properties of the X-chromosome inactivation centre. Herzing, L.B., Romer, J.T., Horn, J.M., Ashworth, A. Nature (1997) [Pubmed]
  13. A 94 kb genomic sequence 3' to the murine Xist gene reveals an AT rich region containing a new testis specific gene Tsx. Simmler, M.C., Cunningham, D.B., Clerc, P., Vermat, T., Caudron, B., Cruaud, C., Pawlak, A., Szpirer, C., Weissenbach, J., Claverie, J.M., Avner, P. Hum. Mol. Genet. (1996) [Pubmed]
  14. Methylation of histone H3 at Lys-9 is an early mark on the X chromosome during X inactivation. Heard, E., Rougeulle, C., Arnaud, D., Avner, P., Allis, C.D., Spector, D.L. Cell (2001) [Pubmed]
  15. Gamete-specific methylation correlates with imprinting of the murine Xist gene. Ariel, M., Robinson, E., McCarrey, J.R., Cedar, H. Nat. Genet. (1995) [Pubmed]
  16. Synergism of Xist RNA, DNA methylation, and histone hypoacetylation in maintaining X chromosome inactivation. Csankovszki, G., Nagy, A., Jaenisch, R. J. Cell Biol. (2001) [Pubmed]
  17. In vivo ultraviolet and dimethyl sulfate footprinting of the 5' region of the expressed and silent Xist alleles. Komura, J., Sheardown, S.A., Brockdorff, N., Singer-Sam, J., Riggs, A.D. J. Biol. Chem. (1997) [Pubmed]
  18. Methylation status of CpG sites and methyl-CpG binding proteins are involved in the promoter regulation of the mouse Xist gene. Allaman-Pillet, N., Djemaï, A., Bonny, C., Schorderet, D.F. Gene Expr. (1998) [Pubmed]
  19. Mbd2 contributes to DNA methylation-directed repression of the Xist gene. Barr, H., Hermann, A., Berger, J., Tsai, H.H., Adie, K., Prokhortchouk, A., Hendrich, B., Bird, A. Mol. Cell. Biol. (2007) [Pubmed]
  20. A transient heterochromatic state in Xist preempts X inactivation choice without RNA stabilization. Sun, B.K., Deaton, A.M., Lee, J.T. Mol. Cell (2006) [Pubmed]
  21. Xite, X-inactivation intergenic transcription elements that regulate the probability of choice. Ogawa, Y., Lee, J.T. Mol. Cell (2003) [Pubmed]
  22. Compact chromatin packaging of inactive X chromosome involves the actively transcribed Xist gene. Endo, Y., Watanabe, T., Mishima, Y., Yoshimura, A., Takagi, N., Kominami, R. Mamm. Genome (1999) [Pubmed]
  23. De novo DNA methylation is dispensable for the initiation and propagation of X chromosome inactivation. Sado, T., Okano, M., Li, E., Sasaki, H. Development (2004) [Pubmed]
  24. Mouse Xist expression begins at zygotic genome activation and is timed by a zygotic clock. Zuccotti, M., Boiani, M., Ponce, R., Guizzardi, S., Scandroglio, R., Garagna, S., Redi, C.A. Mol. Reprod. Dev. (2002) [Pubmed]
  25. Chromatin structure analysis of the mouse Xist locus. McCabe, V., Formstone, E.J., O'Neill, L.P., Turner, B.M., Brockdorff, N. Proc. Natl. Acad. Sci. U.S.A. (1999) [Pubmed]
  26. Comparison of gene expression in male and female mouse blastocysts revealed imprinting of the X-linked gene, Rhox5/Pem, at preimplantation stages. Kobayashi, S., Isotani, A., Mise, N., Yamamoto, M., Fujihara, Y., Kaseda, K., Nakanishi, T., Ikawa, M., Hamada, H., Abe, K., Okabe, M. Curr. Biol. (2006) [Pubmed]
  27. Characterization of mouse Dach2, a homologue of Drosophila dachshund. Davis, R.J., Shen, W., Sandler, Y.I., Heanue, T.A., Mardon, G. Mech. Dev. (2001) [Pubmed]
  28. Transient homologous chromosome pairing marks the onset of X inactivation. Xu, N., Tsai, C.L., Lee, J.T. Science (2006) [Pubmed]
  29. Cloning and characterization of a murine brain specific gene Bpx and its human homologue lying within the Xic candidate region. Rougeulle, C., Avner, P. Hum. Mol. Genet. (1996) [Pubmed]
  30. Control of Xist expression for imprinted and random X chromosome inactivation in mice. Matsui, J., Goto, Y., Takagi, N. Hum. Mol. Genet. (2001) [Pubmed]
  31. Differential pattern of Xist RNA accumulation in single blastomeres isolated from 8-cell stage mouse embryos following laser zona drilling. Hartshorn, C., Rice, J.E., Wangh, L.J. Mol. Reprod. Dev. (2003) [Pubmed]
  32. Developmentally-regulated changes of Xist RNA levels in single preimplantation mouse embryos, as revealed by quantitative real-time PCR. Hartshorn, C., Rice, J.E., Wangh, L.J. Mol. Reprod. Dev. (2002) [Pubmed]
  33. Requirement for Xist in X chromosome inactivation. Penny, G.D., Kay, G.F., Sheardown, S.A., Rastan, S., Brockdorff, N. Nature (1996) [Pubmed]
 
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