Polycomb proteins targeted by a short repeat RNA to the mouse X chromosome

Jing Zhao, Bryan K. Sun, Jennifer A. Erwin, Ji Joon Song, Jeannie T. Lee

Research output: Contribution to journalArticlepeer-review

1160 Scopus citations

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.

Original languageEnglish (US)
Pages (from-to)750-756
Number of pages7
JournalScience
Volume322
Issue number5902
DOIs
StatePublished - Oct 31 2008
Externally publishedYes

ASJC Scopus subject areas

  • General

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