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

Abstract

In mammals, X-inactivation silences one of two female X chromosomes. Silencing depends on the noncoding gene, Xist ( i nactive X - s pecific t 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.