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Xist has properties of the X-chromosome inactivation centre

Abstract

X-chromosome inactivation is the process by which female mammals (with two X chromosomes) achieve expression of X-chromosomal genes equivalent to that of males (one X and one Y chromosome)1,2. This results in the transcriptional silencing of virtually all genes on one of the X chromosomes in female somatic cells. X-chromosome inactivation has been shown to act in cis and to initiate and spread from a single site on the X chromosome known as the X-inactivation centre (Xic)2,3. The Xic has been localized to a 450-kilobase region of the mouse X chromosome4. The Xist gene also maps to this region and is expressed exclusively from the inactive X chromosome3–7. Xist is unusual in that it appears not to code for a protein but produces a nuclear RNA which colocalizes with the inactive X chromosome4,8. 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 cis9. Here we show that Xist, introduced onto an autosome, is sufficient by itself for inactivation in cis and that Xist RNA becomes localized close to the autosome into which the gene is integrated. In addition, the presence of autosomal Xist copies leads to activation of the endogeneous Xist gene in some cells, suggesting that elements required for some aspects of chromosome counting are contained within the construct. Thus the Xist gene exhibits properties of the X-inactivation centre.

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References

  1. Lyon, M. F. Gene action in the X chromosome of the mouse (Mus musculus L.). Nature 190, 370–373 (1961).

    Article  ADS  Google Scholar 

  2. Lyon, M. F. Some milestones in the history of X-chromosome inactivation. Annu. Rev. Genet. 26, 16–28 (1992).

    Article  CAS  Google Scholar 

  3. Rastan, S. X Chromosome inactivation and the Xist gene. Curr. Opin. Genet. Dev. 4, 292–297 (1994).

    Article  CAS  Google Scholar 

  4. Lee, J. T., Strauss, W. M., Dausman, J. A. & Jaenisch, R. A 450 kb transgene displays properties of the mammalian X-inactivation center. Cell 86, 83–94 (1996).

    Article  CAS  Google Scholar 

  5. Brown, C. J. et al. A gene from the region of the human X-inactivation centre is expressed exclusively from the inactive X chromosome. Nature 349, 38–44 (1991).

    Article  ADS  CAS  Google Scholar 

  6. Brockdorff, N. et al. Conservation of position and exclusive expression of mouse Xist from the inactive X chromosome. Nature 351, 329–331 (1991).

    Article  ADS  CAS  Google Scholar 

  7. Borsani, G. et al. Characterization of a murine gene expressed from the inactive X chromosome. Nature 351, 325–329 (1991).

    Article  ADS  CAS  Google Scholar 

  8. Clemson, C. M., McNeil, J. A., Willard, H. F. & Lawrence, J. B. XIST RNA paints the inactive X chromosome at interphase: evidence for a novel RNA involved in nuclear/chromosome structure. J. Cell Biol. 132, 259–275 (1996).

    Article  CAS  Google Scholar 

  9. Penny, G. D., Kay, G. F., Sheardown, S. A., Rastan, S. & Brockdorff, N. Requirement for Xist in X chromosome inactivation. Nature 379, 131–137 (1996).

    Article  ADS  CAS  Google Scholar 

  10. Rastan, S. & Robertson, E. J. X-chromosome deletions in embryo-derived (EK) cell lines associated with lack of X-chromosome inactivation. J. Embryol. Exp. Morphol. 90, 379–388 (1985).

    CAS  PubMed  Google Scholar 

  11. Rastan, S. Primary non-random X inactivation caused by controlling elements in the mouse demonstrated at the cellular level. Genet. Res. 40, 139–147 (1982).

    Article  CAS  Google Scholar 

  12. Herzing, L. & Ashworth, A. Construction of specific cosmids from YACs by homologous recombination in yeast. Nucleic Acids Res. 23, 4005–4006 (1995).

    Article  CAS  Google Scholar 

  13. Tan, S.-S., Williams, E. A. & Tarn, P. P. L. X chromosome inactivation occurs at different times in different tissues of the post-implantation mouse embryo. Nature Genet. 3, 170–174 (1993).

    Article  CAS  Google Scholar 

  14. Matsuura, S., Episkopou, V., Hamvas, R. & Brown, S. Xist expression from an Xist YAC transgene carried on the mouse Y chromosome. Hum. Molec. Genet. 3, 451–459 (1996).

    Article  Google Scholar 

  15. Kay, G. F. et al. Expression of Xist during mouse development suggests a role in the initiation of X chromosome inactivation. Cell 72, 171–182 (1993).

    Article  CAS  Google Scholar 

  16. Palmiter, R. D. & Brinster, R. L. Germ-line transformation of mice. Annu. Rev. Genet. 20, 465–499 (1986).

    Article  CAS  Google Scholar 

  17. Hendrich, B. D., Brown, C. J. & Willard, H. F. Evolutionary conservation of possible functional domains of the human and murine XIST genes. Hum. Molec. Genet. 2, 663–672 (1993).

    Article  CAS  Google Scholar 

  18. Jeppesen, P. & Turner, B. M. The inactive X chromosome in female mammals is distinguished by a lack of histone H4 acetylation, a cytogenetic marker for gene expression. Cell 74, 281–289 (1993).

    Article  CAS  Google Scholar 

  19. RamirezSolis, R., Liu, P. & Bradley, A. Chromosome engineering in mice. Nature 378, 720–724 (1995).

    Article  ADS  CAS  Google Scholar 

  20. Gautier, C., Mehtali, M. & Lathe, R. A ubiquitous mammalian expression vector, pHMG, based on a housekeeping gene promoter. Nucleic Acids Res. 17, 8389 (1989).

    Article  CAS  Google Scholar 

  21. Friedrich, G. & Soriano, P. Promoter traps in embryonic stem cells: a genetic screen to identify and mutate developmental genes in mice. Genes Dev. 5, 1513–1523 (1991).

    Article  CAS  Google Scholar 

  22. Herzing, L. & Meyn, M. S. Novel lacZ-based recombination vectors for mammalian cells. Gene 137, 163–169 (1993).

    Article  CAS  Google Scholar 

  23. Lehrach, H. et al. in Genome Analysis 1: Genetic and Physical Mapping (eds Davies, K. E. & Tilghman, S. M.) 39–81 (Cold Spring Harbor Laboratory Press, Cold Spring Harbor, New York, 1990).

    Google Scholar 

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Herzing, L., Romer, J., Horn, J. et al. Xist has properties of the X-chromosome inactivation centre. Nature 386, 272–275 (1997). https://doi.org/10.1038/386272a0

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