title: Polycomb proteins targeted by a short repeat RNA to the mouse X chromosome.
abstract: To equalize X-chromosome dosages between the sexes, the female mammal inactivates one of her two X chromosomes. X-chromosome inactivation (XCI) is initiated by expression of Xist, a 17-kb noncoding RNA (ncRNA) that accumulates on the X in cis. Because interacting factors have not been isolated, the mechanism by which Xist induces silencing remains unknown. We discovered a 1.6-kilobase ncRNA (RepA) within Xist and identified the Polycomb complex, PRC2, as its direct target. PRC2 is initially recruited to the X by RepA RNA, with Ezh2 serving as the RNA binding subunit. The antisense Tsix RNA inhibits this interaction. RepA depletion abolishes full-length Xist induction and trimethylation on lysine 27 of histone H3 of the X. Likewise, PRC2 deficiency compromises Xist up-regulation. Therefore, RepA, together with PRC2, is required for the initiation and spread of XCI. We conclude that a ncRNA cofactor recruits Polycomb complexes to their target locus.
authors.affiliation: Howard Hughes Medical Institute, Boston, MA 02115, USA.
authors.forename: Jing
authors.initials: J
authors.lastname: Zhao
authors.forename: Bryan K
authors.initials: BK
authors.lastname: Sun
authors.forename: Jennifer A
authors.initials: JA
authors.lastname: Erwin
authors.forename: Ji-Joon
authors.initials: JJ
authors.lastname: Song
authors.forename: Jeannie T
authors.initials: JT
authors.lastname: Lee
mesh_terms: D000818:Animals; D002454:Cell Differentiation; D002460:Cell Line; D047369:Chromatin Immunoprecipitation; D024202:Electrophoretic Mobility Shift Assay; D053595:Embryonic Stem Cells; D005260:Female; D005347:Fibroblasts; D008297:Male; D051379:Mice; D008822:Mice, Transgenic; D008969:Molecular Sequence Data; D063146:Polycomb-Group Proteins; D016133:Polymerase Chain Reaction; D062085:RNA, Long Noncoding; D022661:RNA, Untranslated / Q000235:genetics / Q000378:metabolism*; D012091:Repetitive Sequences, Nucleic Acid; D012097:Repressor Proteins / Q000378:metabolism*; D015854:Up-Regulation; D014960:X Chromosome / Q000378:metabolism*; D049951:X Chromosome Inactivation
chemical_list: D063146:Polycomb-Group Proteins; D062085:RNA, Long Noncoding; D022661:RNA, Untranslated; D012097:Repressor Proteins; C077885:XIST non-coding RNA