<i>Tsix</i>-mediated epigenetic switch of a CTCF-flanked region of the <i>Xist</i> promoter determines the <i>Xist</i> transcription program

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<jats:p>Initiation of X inactivation depends on the coordinated expression of the sense/antisense pair <jats:italic>Xist</jats:italic>/<jats:italic>Tsix</jats:italic>. We show here that a precisely defined <jats:italic>Xist</jats:italic> promoter region flanked by CTCF is maintained by <jats:italic>Tsix</jats:italic> in a heterochromatic-like state in undifferentiated embryonic stem (ES) cells and shifts to a pseudoeuchromatic structure upon <jats:italic>Tsix</jats:italic> truncation. We further demonstrate that the epigenetic state of the <jats:italic>Xist</jats:italic> 5′ region prior to differentiation predicts the efficiency of transcriptional machinery recruitment to the <jats:italic>Xist</jats:italic> promoter during differentiation. Our results provide mechanistic insights into the <jats:italic>Tsix</jats:italic>-mediated epigenetic regulation of <jats:italic>Xist</jats:italic> resulting in <jats:italic>Xist</jats:italic> promoter activation and initiation of X inactivation in differentiating ES cells.</jats:p>

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  • Genes & Development

    Genes & Development 20 (20), 2787-2792, 2006-10-15

    Cold Spring Harbor Laboratory

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