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Originally published in Science Express on 6 December 2001
Science 11 January 2002:
Vol. 295. no. 5553, pp. 345 - 347
DOI: 10.1126/science.1065982
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Reports

CTCF, a Candidate Trans-Acting Factor for X-Inactivation Choice

Wendy Chao, Khanh D. Huynh, Rebecca J. Spencer, Lance S. Davidow, Jeannie T. Lee*

In mammals, X-inactivation silences one of two female X chromosomes. Silencing depends on the noncoding gene, Xist (nactive -pecific ranscript), and is blocked by the antisense gene, Tsix. Deleting the choice/imprinting center in Tsix affects X-chromosome selection. Here, we identify the insulator and transcription factor, CTCF, as a candidate trans-acting factor for X-chromosome selection. The choice/imprinting center contains tandem CTCF binding sites that function in an enhancer-blocking assay. In vitro binding is reduced by CpG methylation and abolished by including non-CpG methylation. We postulate that Tsix and CTCF together establish a regulatable epigenetic switch for X-inactivation.

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}frodo.mgh.harvard.edu

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