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

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Science  11 Jan 2002:
Vol. 295, Issue 5553, pp. 345-347
DOI: 10.1126/science.1065982

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In mammals, X-inactivation silences one of two female X chromosomes. Silencing depends on the noncoding gene, Xist(inactive X-specifictranscript), and is blocked by the antisense gene,Tsix. Deleting the choice/imprinting center inTsix affects X-chromosome selection. Here, we identify the insulator and transcription factor, CTCF, as a candidatetrans-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.

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