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Originally published in Science Express on 19 January 2006
Science 24 February 2006:
Vol. 311. no. 5764, pp. 1149 - 1152
DOI: 10.1126/science.1122984
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Reports

Transient Homologous Chromosome Pairing Marks the Onset of X Inactivation

Na Xu, Chia-Lun Tsai, Jeannie T. Lee*

Mammalian X inactivation turns off one female X chromosome to enact dosage compensation between XX and XY individuals. X inactivation is known to be regulated in cis by Xite, Tsix, and Xist, but in principle the two Xs must also be regulated in trans to ensure mutually exclusive silencing. Here, we demonstrate that interchromosomal pairing mediates this communication. Pairing occurs transiently at the onset of X inactivation and is specific to the X-inactivation center. Deleting Xite and Tsix perturbs pairing and counting/choice, whereas their autosomal insertion induces de novo X-autosome pairing. Ectopic X-autosome interactions inhibit endogenous X-X pairing and block the initiation of X-chromosome inactivation. Thus, Tsix and Xite function both in cis and in trans. We propose that Tsix and Xite regulate counting and mutually exclusive choice through X-X pairing.

Howard Hughes Medical Institute, Department of Molecular Biology, Massachusetts General Hospital, Department of Genetics, Harvard Medical School Boston, MA 02114, USA.

* To whom correspondence should be addressed. E-mail: lee{at}molbio.mgh.harvard.edu

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