CTCF, a candidate trans-acting factor for X-inactivation choice

  • Science. 2002 Jan 11;295(5553):345-7. doi: 10.1126/science.1065982.
Wendy Chao  1 ,  Khanh D Huynh ,  Rebecca J Spencer ,  Lance S Davidow ,  Jeannie T Lee
Affiliations
  • 1. Howard Hughes Medical Institute, Department of Molecular Biology, Massachusetts General Hospital, Department of Genetics, Harvard Medical School, Boston, MA 02114, USA.
PMID: 11743158 DOI: 10.1126/science.1065982
Abstract

In mammals, X-inactivation silences one of two female X chromosomes. Silencing depends on the noncoding gene, Xist (inactive X-specific transcript), 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.