Polycomb proteins targeted by a short repeat RNA to the mouse X chromosome.
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.
Zhao
Jing
J
Howard Hughes Medical Institute, Boston, MA 02115, USA.
Sun
Bryan K
BK
Erwin
Jennifer A
JA
Song
Ji-Joon
JJ
Lee
Jeannie T
JT
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
D063146:Polycomb-Group Proteins; D062085:RNA, Long Noncoding; D022661:RNA, Untranslated; D012097:Repressor Proteins; C077885:XIST non-coding RNA