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.
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We thank R. Spencer and Y. Jeon for unpublished data and technical advice and Y. Ogawa for critical reading of the manuscript. Grant support: Massachusetts General Hospital Fund for Medical Discovery (J.Z.), NSF predoctoral award (J.A.E.), Jane Coffin Childs Fellowship (J.J.S.), and NIH-R01GM58839 (J.T.L.). J.T.L. is an Investigator of the HHMI. The transcript “RepA†for Repeat A has GenBank accession number FJ361197.
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Science
Volume 322 | Issue 5902
31 October 2008
31 October 2008
Copyright
American Association for the Advancement of Science.
Submission history
Received: 10 July 2008
Accepted: 19 September 2008
Published in print: 31 October 2008
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