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. 1995 Apr 11;92(8):3531–3535. doi: 10.1073/pnas.92.8.3531

Xce haplotypes show modified methylation in a region of the active X chromosome lying 3' to Xist.

B Courtier 1, E Heard 1, P Avner 1
PMCID: PMC42201  PMID: 7536936

Abstract

During early mammalian embryogenesis, one of the two X chromosomes in somatic cells of the female becomes inactivated through a process that is thought to depend on a unique initiator region, the X-chromosome inactivation center (Xic). The recently characterized Xist sequence (X-inactive-specific transcript) is thought to be a possible candidate for Xic. In mice a further genetic element, the X chromosome-controlling element (Xce), is also known to influence the choice of which of the two X chromosomes is inactivated. We report that a region of the mouse X chromosome lying 15 kb distal to Xist contains several sites that show hypermethylation specifically associated with the active X chromosome. Analysis of this region in various Xce strains has revealed a correlation between the strength of the Xce allele carried and the methylation status of this region. We propose that such a region could be involved in the initial stages of the inactivation process and in particular in the choice of which of the two X chromosomes present in a female cell will be inactivated.

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Selected References

These references are in PubMed. This may not be the complete list of references from this article.

  1. Barlow D. P. Imprinting: a gamete's point of view. Trends Genet. 1994 Jun;10(6):194–199. doi: 10.1016/0168-9525(94)90255-0. [DOI] [PubMed] [Google Scholar]
  2. Borsani G., Tonlorenzi R., Simmler M. C., Dandolo L., Arnaud D., Capra V., Grompe M., Pizzuti A., Muzny D., Lawrence C. Characterization of a murine gene expressed from the inactive X chromosome. Nature. 1991 May 23;351(6324):325–329. doi: 10.1038/351325a0. [DOI] [PubMed] [Google Scholar]
  3. Brockdorff N., Ashworth A., Kay G. F., Cooper P., Smith S., McCabe V. M., Norris D. P., Penny G. D., Patel D., Rastan S. Conservation of position and exclusive expression of mouse Xist from the inactive X chromosome. Nature. 1991 May 23;351(6324):329–331. doi: 10.1038/351329a0. [DOI] [PubMed] [Google Scholar]
  4. Brockdorff N., Ashworth A., Kay G. F., McCabe V. M., Norris D. P., Cooper P. J., Swift S., Rastan S. 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 Oct 30;71(3):515–526. doi: 10.1016/0092-8674(92)90519-i. [DOI] [PubMed] [Google Scholar]
  5. Brown C. J., Ballabio A., Rupert J. L., Lafreniere R. G., Grompe M., Tonlorenzi R., Willard H. F. A gene from the region of the human X inactivation centre is expressed exclusively from the inactive X chromosome. Nature. 1991 Jan 3;349(6304):38–44. doi: 10.1038/349038a0. [DOI] [PubMed] [Google Scholar]
  6. Cattanach B. M., Perez J. N., Pollard C. E. Controlling elements in the mouse X-chromosome. II. Location in the linkage map. Genet Res. 1970 Apr;15(2):183–195. doi: 10.1017/s0016672300001518. [DOI] [PubMed] [Google Scholar]
  7. Cattanach B. M., Rasberry C., Evans E. P., Dandolo L., Simmler M. C., Avner P. Genetic and molecular evidence of an X-chromosome deletion spanning the tabby (Ta) and testicular feminization (Tfm) loci in the mouse. Cytogenet Cell Genet. 1991;56(3-4):137–143. doi: 10.1159/000133070. [DOI] [PubMed] [Google Scholar]
  8. Cattanach B. M., Williams C. E. Evidence of non-random X chromosome activity in the mouse. Genet Res. 1972 Jun;19(3):229–240. doi: 10.1017/s001667230001449x. [DOI] [PubMed] [Google Scholar]
  9. Heard E., Simmler M. C., Larin Z., Rougeulle C., Courtier B., Lehrach H., Avner P. Physical mapping and YAC contig analysis of the region surrounding Xist on the mouse X chromosome. Genomics. 1993 Mar;15(3):559–569. doi: 10.1006/geno.1993.1108. [DOI] [PubMed] [Google Scholar]
  10. Jeffreys A. J., MacLeod A., Tamaki K., Neil D. L., Monckton D. G. Minisatellite repeat coding as a digital approach to DNA typing. Nature. 1991 Nov 21;354(6350):204–209. doi: 10.1038/354204a0. [DOI] [PubMed] [Google Scholar]
  11. Johnston P. G., Cattanach B. M. Controlling elements in the mouse. IV. Evidence of non-random X-inactivation. Genet Res. 1981 Apr;37(2):151–160. doi: 10.1017/s0016672300020127. [DOI] [PubMed] [Google Scholar]
  12. Kay G. F., Penny G. D., 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. 1993 Jan 29;72(2):171–182. doi: 10.1016/0092-8674(93)90658-d. [DOI] [PubMed] [Google Scholar]
  13. LYON M. F., SEARLE A. G., FORD C. E., OHNO S. A MOUSE TRANSLOCATION SUPPRESSING SEX-LINKED VARIEGATION. Cytogenetics. 1964;3:306–323. doi: 10.1159/000129820. [DOI] [PubMed] [Google Scholar]
  14. Leppig K. A., Brown C. J., Bressler S. L., Gustashaw K., Pagon R. A., Willard H. F., Disteche C. M. Mapping of the distal boundary of the X-inactivation center in a rearranged X chromosome from a female expressing XIST. Hum Mol Genet. 1993 Jul;2(7):883–887. doi: 10.1093/hmg/2.7.883. [DOI] [PubMed] [Google Scholar]
  15. Lyon M. F. Epigenetic inheritance in mammals. Trends Genet. 1993 Apr;9(4):123–128. doi: 10.1016/0168-9525(93)90206-w. [DOI] [PubMed] [Google Scholar]
  16. Monk M. Methylation and the X chromosome. Bioessays. 1986 May;4(5):204–208. doi: 10.1002/bies.950040505. [DOI] [PubMed] [Google Scholar]
  17. Norris D. P., Patel D., Kay G. F., Penny G. D., Brockdorff N., Sheardown S. A., Rastan S. Evidence that random and imprinted Xist expression is controlled by preemptive methylation. Cell. 1994 Apr 8;77(1):41–51. doi: 10.1016/0092-8674(94)90233-x. [DOI] [PubMed] [Google Scholar]
  18. Riggs A. D., Pfeifer G. P. X-chromosome inactivation and cell memory. Trends Genet. 1992 May;8(5):169–174. doi: 10.1016/0168-9525(92)90219-t. [DOI] [PubMed] [Google Scholar]
  19. Rougeulle C., Colleaux L., Dujon B., Avner P. Generation and characterization of an ordered lambda clone array for the 460-kb region surrounding the murine Xist sequence. Mamm Genome. 1994 Jul;5(7):416–423. doi: 10.1007/BF00357001. [DOI] [PubMed] [Google Scholar]
  20. Simmler M. C., Cattanach B. M., Rasberry C., Rougeulle C., Avner P. Mapping the murine Xce locus with (CA)n repeats. Mamm Genome. 1993 Sep;4(9):523–530. doi: 10.1007/BF00364788. [DOI] [PubMed] [Google Scholar]

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