title: A prominent and conserved role for YY1 in Xist transcriptional activation.
abstract: Accumulation of the noncoding RNA Xist on one X chromosome in female cells is a hallmark of X-chromosome inactivation (XCI) in eutherians. Here we uncover an essential function for the ubiquitous autosomal transcription factor Yin-Yang 1 (YY1) in the transcriptional activation of Xist in both human and mouse. We show that loss of YY1 prevents Xist upregulation during the initiation and maintenance of X-inactivation, and that YY1 binds directly the Xist 5' region to trigger the activity of the Xist promoter. Binding of YY1 to the Xist 5' region before XCI competes with the Xist repressor REX1, whereas DNA methylation controls mono-allelic fixation of YY1 to Xist at the onset of XCI. YY1 is thus the first autosomal activating factor involved in a fundamental and conserved pathway of Xist regulation that ensures the asymmetric transcriptional upregulation of the master regulator of XCI.
authors.affiliation: CNRS, UMR7216 Epigenetics and Cell Fate, F-75013 Paris, France.|Univ Paris Diderot, Sorbonne Paris Cité, F-75013 Paris, France.
authors.forename: Mélanie
authors.initials: M
authors.lastname: Makhlouf
authors.affiliation: CNRS, UMR7216 Epigenetics and Cell Fate, F-75013 Paris, France.|Univ Paris Diderot, Sorbonne Paris Cité, F-75013 Paris, France.
authors.forename: Jean-François
authors.initials: JF
authors.lastname: Ouimette
authors.affiliation: CNRS, UMR7216 Epigenetics and Cell Fate, F-75013 Paris, France.|Univ Paris Diderot, Sorbonne Paris Cité, F-75013 Paris, France.|NIEHS, Laboratory of Molecular Carcinogenesis, Research Triangle Park, NC, USA (Current address).
authors.forename: Andrew
authors.initials: A
authors.lastname: Oldfield
authors.affiliation: Institute Pasteur, Paris, France.
authors.forename: Pablo
authors.initials: P
authors.lastname: Navarro
authors.affiliation: CNRS, UMR7216 Epigenetics and Cell Fate, F-75013 Paris, France.|Univ Paris Diderot, Sorbonne Paris Cité, F-75013 Paris, France.
authors.forename: Damien
authors.initials: D
authors.lastname: Neuillet
authors.affiliation: CNRS, UMR7216 Epigenetics and Cell Fate, F-75013 Paris, France.|Univ Paris Diderot, Sorbonne Paris Cité, F-75013 Paris, France.
authors.forename: Claire
authors.initials: C
authors.lastname: Rougeulle
mesh_terms: D000818:Animals; D002460:Cell Line; D002478:Cells, Cultured; D019175:DNA Methylation; D005260:Female; D006801:Humans; D051379:Mice; D011401:Promoter Regions, Genetic; D062085:RNA, Long Noncoding / Q000235:genetics* / Q000378:metabolism; D012097:Repressor Proteins / Q000378:metabolism; D015854:Up-Regulation; D049951:X Chromosome Inactivation / Q000235:genetics*; D050986:YY1 Transcription Factor / Q000378:metabolism*
chemical_list: D062085:RNA, Long Noncoding; D012097:Repressor Proteins; C077885:XIST non-coding RNA; D050986:YY1 Transcription Factor