title: Tsix transcription across the Xist gene alters chromatin conformation without affecting Xist transcription: implications for X-chromosome inactivation.
abstract: X-chromosome inactivation (XCI) is highly dynamic during early mouse embryogenesis and strictly depends on the Xist noncoding RNA. The regulation of Xist and its antisense partner Tsix remains however poorly understood. We provide here the first evidence of transcriptional control of Xist expression. We show that RNA polymerase II (RNAPolII) preinitiation complex recruitment and H3 Lys 4 (H3-K4) methylation at the Xist promoter form the basis of the Xist expression profiles that drives both imprinted and random XCI. In embryonic stem (ES) cells, which are derived from the inner cell mass where imprinted XCI is reversed and both Xs are active, we show that Xist is repressed at the level of preinitiation complex (PIC) recruitment. We further demonstrate that Tsix, although highly transcribed in ES cells, is not itself responsible for the transcriptional down-regulation of Xist. Rather, Tsix induces efficient H3-K4 methylation over the entire Xist/Tsix unit. We suggest that chromatin remodeling of the Xist locus induced by biallelic Tsix transcription renders both Xist loci epigenetically equivalent and equally competent for transcription. In this model, Tsix, by resetting the epigenetic state of the Xist/Tsix locus, mediates the transition from imprinted to random XCI.
authors.affiliation: Unité de Génétique Moléculaire Murine, URA 2578, Pasteur Institute, 75724 Paris Cedex 15, France.
authors.forename: Pablo
authors.initials: P
authors.lastname: Navarro
authors.forename: Sylvain
authors.initials: S
authors.lastname: Pichard
authors.forename: Constance
authors.initials: C
authors.lastname: Ciaudo
authors.forename: Philip
authors.initials: P
authors.lastname: Avner
authors.forename: Claire
authors.initials: C
authors.lastname: Rougeulle
mesh_terms: D000483:Alleles; D000818:Animals; D002454:Cell Differentiation; D002478:Cells, Cultured; D002843:Chromatin / Q000737:chemistry / Q000235:genetics / Q000378:metabolism; D042002:Chromatin Assembly and Disassembly / Q000235:genetics*; D004303:Dosage Compensation, Genetic; D047108:Embryonic Development / Q000235:genetics; D044127:Epigenesis, Genetic; D005260:Female; D018507:Gene Expression Regulation, Developmental; D006657:Histones / Q000737:chemistry / Q000378:metabolism; D008297:Male; D051379:Mice; D008957:Models, Genetic; D008968:Molecular Conformation; D062085:RNA, Long Noncoding; D022661:RNA, Untranslated / Q000235:genetics*; D014157:Transcription Factors / Q000235:genetics*; D014158:Transcription, Genetic
chemical_list: D002843:Chromatin; D006657:Histones; D062085:RNA, Long Noncoding; D022661:RNA, Untranslated; D014157:Transcription Factors; C465658:Tsix transcript, mouse; C077885:XIST non-coding RNA