title: A boundary element between Tsix and Xist binds the chromatin insulator Ctcf and contributes to initiation of X-chromosome inactivation.
abstract: In mammals, X-chromosome inactivation (XCI) equalizes X-linked gene expression between XY males and XX females and is controlled by a specialized region known as the X-inactivation center (Xic). The Xic harbors two chromatin interaction domains, one centered around the noncoding Xist gene and the other around the antisense Tsix counterpart. Previous work demonstrated the existence of a chromatin transitional zone between the two domains. Here, we investigate the region and discover a conserved element, RS14, that presents a strong binding site for Ctcf protein. RS14 possesses an insulatory function suggestive of a boundary element and is crucial for cell differentiation and growth. Knocking out RS14 results in compromised Xist induction and aberrant XCI in female cells. These data demonstrate that a junction element between Tsix and Xist contributes to the initiation of XCI.
authors.affiliation: Howard Hughes Medical Institute, Department of Molecular Biology, Massachusetts General Hospital, Department of Genetics, Harvard Medical School, Boston, Massachusetts 02114, USA.
authors.forename: Rebecca J
authors.initials: RJ
authors.lastname: Spencer
authors.forename: Brian C
authors.initials: BC
authors.lastname: del Rosario
authors.forename: Stefan F
authors.initials: SF
authors.lastname: Pinter
authors.forename: Derek
authors.initials: D
authors.lastname: Lessing
authors.forename: Ruslan I
authors.initials: RI
authors.lastname: Sadreyev
authors.forename: Jeannie T
authors.initials: JT
authors.lastname: Lee
mesh_terms: D000818:Animals; D001483:Base Sequence; D001665:Binding Sites; D000076246:CCCTC-Binding Factor; D002460:Cell Line; D002843:Chromatin / Q000235:genetics* / Q000378:metabolism; D047369:Chromatin Immunoprecipitation; D024202:Electrophoretic Mobility Shift Assay; D005260:Female; D015870:Gene Expression; D017404:In Situ Hybridization, Fluorescence; D038101:Insulator Elements / Q000235:genetics*; D008297:Male; D051379:Mice; D057507:Mice, 129 Strain; D008969:Molecular Sequence Data; D009154:Mutation; D011485:Protein Binding; D062085:RNA, Long Noncoding; D022661:RNA, Untranslated / Q000235:genetics* / Q000378:metabolism; D012097:Repressor Proteins / Q000235:genetics* / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction; D012689:Sequence Homology, Nucleic Acid; D049951:X Chromosome Inactivation
chemical_list: D000076246:CCCTC-Binding Factor; D002843:Chromatin; C000619698:Ctcf protein, mouse; D062085:RNA, Long Noncoding; D022661:RNA, Untranslated; D012097:Repressor Proteins; C465658:Tsix transcript, mouse; C077885:XIST non-coding RNA