Comparative Sequence Analysis of the X-Inactivation Center Region in Mouse, Human, and Bovine

Citations Over Time

Abstract

We have sequenced to high levels of accuracy 714-kb and 233-kb regions of the mouse and bovine X-inactivation centers (Xic), respectively, centered on the Xist gene. This has provided the basis for a fully annotated comparative analysis of the mouse Xic with the 2.3-Mb orthologous region in human and has allowed a three-way species comparison of the core central region, including the Xist gene. These comparisons have revealed conserved genes, both coding and noncoding, conserved CpG islands and, more surprisingly, conserved pseudogenes. The distribution of repeated elements, especially LINE repeats, in the mouse Xic region when compared to the rest of the genome does not support the hypothesis of a role for these repeat elements in the spreading of X inactivation. Interestingly, an asymmetric distribution of LINE elements on the two DNA strands was observed in the three species, not only within introns but also in intergenic regions. This feature is suggestive of important transcriptional activity within these intergenic regions. In silico prediction followed by experimental analysis has allowed four new genes, Cnbp2, Ftx, Jpx, and Ppnx, to be identified and novel, widespread, complex, and apparently noncoding transcriptional activity to be characterized in a region 5' of Xist that was recently shown to attract histone modification early after the onset of X inactivation.

Related Papers

• → A promoter mutation in the XIST gene in two unrelated families with skewed X-chromosome inactivation(1997)295 cited
• → Xist has properties of the X-chromosome inactivation centre(1997)250 cited
• → Expression of the X–inactivation–associated gene XIST during spermatogenesis(1992)140 cited
• → A male with two contiguous inactivation centers on a single X chromosome: study of X inactivation and XIST expression(1992)20 cited
• → Xist and X chromosome inactivation(1998)14 cited