Comparative Sequence Analysis of the X-Inactivation Center Region in Mouse, Human, and Bovine
- Corinne Chureau1,6,
- Marine Prissette1,6,
- Agnès Bourdet1,
- Valérie Barbe2,
- Laurence Cattolico2,
- Louis Jones3,
- André Eggen4,
- Philip Avner1,7, and
- Laurent Duret5
- 1Unité de Génétique Moléculaire Murine, URA CNRS 1947, Institut Pasteur, Paris, France; 2Génoscope, Centre National de Séquençage, Evry, France; 3Pôle informatique, Logiciels et Banques de Données, Institut Pasteur, Paris, France; 4Laboratoire de Génétique Biochimique et de Cytogénétique, INRA-CRJ, Jouy-en-Josas, France; 5Laboratoire de Biométrie et Biologie Evolutive, UMR CNRS 5558, Villeurbanne Cedex, France
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 theXist 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.
[The sequence data described in this paper have been submitted to the EMBL data library under accession nos. AJ421478, AJ421479, AJ421480, andAJ421481. Online supplemental data are available athttp://pbil.univ-lyon1.fr/datasets/Xic2002/data.html andwww.genome.org.]
