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Published online before print June 1, 2002
Genome Research, DOI: 10.1101/gr.GR-1529R
November 21, 2000, 10.1101/gr.GR-1529R
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Vol. 12, Issue 6, 894-908, June 2002

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

Corinne Chureau,1,6 Marine Prissette,1,6 Agnès Bourdet,1 Valérie Barbe,2 Laurence Cattolico,2 Louis Jones,3 André Eggen,4 Philip Avner,1,7 and Laurent Duret5

1 Unité de Génétique Moléculaire Murine, URA CNRS 1947, Institut Pasteur, Paris, France; 2 Génoscope, Centre National de Séquençage, Evry, France; 3 Pôle informatique, Logiciels et Banques de Données, Institut Pasteur, Paris, France; 4 Laboratoire de Génétique Biochimique et de Cytogénétique, INRA-CRJ, Jouy-en-Josas, France; 5 Laboratoire de Biométrie et Biologie Evolutive, UMR CNRS 5558, Villeurbanne Cedex, France

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.

[The sequence data described in this paper have been submitted to the EMBL data library under accession nos. AJ421478, AJ421479, AJ421480, and AJ421481. Online supplemental data are available at http://pbil.univ-lyon1.fr/datasets/Xic2002/data.html and www.genome.org.]

6 These authors contributed equally to this work.

7 Corresponding author.

12:894-908 ©2002 by Cold Spring Harbor Laboratory Press  ISSN 1088-9051/02 $5.00
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