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Science 7 December 2007:
Vol. 318. no. 5856, pp. 1632 - 1636
DOI: 10.1126/science.1149420
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Reports

Sensing X Chromosome Pairs Before X Inactivation via a Novel X-Pairing Region of the Xic

S. Augui,1 G. J. Filion,1 S. Huart,1 E. Nora,1 M. Guggiari,1 M. Maresca,2 A. F. Stewart,2 E. Heard1*

Mammalian dosage compensation involves silencing of one of the two X chromosomes in females and is controlled by the X-inactivation center (Xic). The Xic, which includes Xist and its antisense transcription unit Tsix/Xite, somehow senses the number of X chromosomes and triggers Xist up-regulation from one of the two X chromosomes in females. We found that a segment of the mouse Xic lying several hundred kilobases upstream of Xist brings the two Xics together before the onset of X inactivation. This region can autonomously drive Xic trans-interactions even as an ectopic single-copy transgene. Its introduction into male embryonic stem cells is strongly selected against, consistent with a possible role in trans-activating Xist. We propose that homologous associations driven by this novel X-pairing region (Xpr) of the Xic enable a cell to sense that more than one X chromosome is present and coordinate reciprocal Xist/Tsix expression.

1 CNRS UMR218, Curie Institute, 26 rue d'Ulm, Paris 75005, France.
2 BioInnovationsZentrum, Technical University Dresden, Tatzberg 47-51, D-01307 Dresden, Germany.

* To whom correspondence should be addressed. E-mail: edith.heard{at}curie.fr

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THIS ARTICLE HAS BEEN CITED BY OTHER ARTICLES:
Association between active genes occurs at nuclear speckles and is modulated by chromatin environment.
J. M. Brown, J. Green, R. P. das Neves, H. A.C. Wallace, A. J.H. Smith, J. Hughes, N. Gray, S. Taylor, W. G. Wood, D. R. Higgs, et al. (2008)
J. Cell Biol. 182, 1083-1097
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Science. ISSN 0036-8075 (print), 1095-9203 (online)