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Research Communication

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

Unité de Génétique Moléculaire Murine, Institut Pasteur 75724, Paris Cedex 15, France

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

[Keywords: X inactivation; chromatin modifications; CTCF boundaries; noncoding RNA; antisense transcription; epigenetic regulation]

Received March 30, 2006; revised version accepted August 17, 2006.

E-MAIL rougeull{at}pasteur.fr; FAX 33-1-45-68-8656.

Supplemental material is available at http://www.genesdev.org.

Article is online at http://www.genesdev.org/cgi/doi/10.1101/gad.389006.

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