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.
Publication types
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Research Support, Non-U.S. Gov't
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Research Support, U.S. Gov't, P.H.S.
MeSH terms
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Animals
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Antisense Elements (Genetics)*
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Binding Sites
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CCCTC-Binding Factor
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CpG Islands
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DNA Methylation
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DNA-Binding Proteins / genetics
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DNA-Binding Proteins / metabolism*
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Dosage Compensation, Genetic*
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Enhancer Elements, Genetic
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Gene Silencing*
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Genomic Imprinting
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HeLa Cells
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Humans
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Mice
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Models, Genetic
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RNA, Long Noncoding
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RNA, Untranslated / genetics
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Repressor Proteins*
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Transcription Factors / genetics
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Transcription Factors / metabolism*
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X Chromosome / genetics*
Substances
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Antisense Elements (Genetics)
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CCCTC-Binding Factor
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CTCF protein, human
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Ctcf protein, mouse
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DNA-Binding Proteins
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RNA, Long Noncoding
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RNA, Untranslated
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Repressor Proteins
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Transcription Factors
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XIST non-coding RNA