title: 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 (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.
authors.affiliation: Howard Hughes Medical Institute, Department of Molecular Biology, Massachusetts General Hospital, Department of Genetics, Harvard Medical School, Boston, MA 02114, USA.
authors.forename: Wendy
authors.initials: W
authors.lastname: Chao
authors.forename: Khanh D
authors.initials: KD
authors.lastname: Huynh
authors.forename: Rebecca J
authors.initials: RJ
authors.lastname: Spencer
authors.forename: Lance S
authors.initials: LS
authors.lastname: Davidow
authors.forename: Jeannie T
authors.initials: JT
authors.lastname: Lee
mesh_terms: D000818:Animals; D016375:Antisense Elements (Genetics); D001665:Binding Sites; D000076246:CCCTC-Binding Factor; D018899:CpG Islands; D019175:DNA Methylation; D004268:DNA-Binding Proteins / Q000235:genetics / Q000378:metabolism*; D004303:Dosage Compensation, Genetic; D004742:Enhancer Elements, Genetic; D020868:Gene Silencing; D018392:Genomic Imprinting; D006367:HeLa Cells; D006801:Humans; D051379:Mice; D008957:Models, Genetic; D062085:RNA, Long Noncoding; D022661:RNA, Untranslated / Q000235:genetics; D012097:Repressor Proteins; D014157:Transcription Factors / Q000235:genetics / Q000378:metabolism*; D014960:X Chromosome / Q000235:genetics*
chemical_list: D016375:Antisense Elements (Genetics); D000076246:CCCTC-Binding Factor; C000619697:CTCF protein, human; C000619698:Ctcf protein, mouse; D004268:DNA-Binding Proteins; D062085:RNA, Long Noncoding; D022661:RNA, Untranslated; D012097:Repressor Proteins; D014157:Transcription Factors; C077885:XIST non-coding RNA