Bryan Sun

Publication Details

  • Polycomb Proteins Targeted by a Short Repeat RNA to the Mouse X Chromosome SCIENCE Zhao, J., Sun, B. K., Erwin, J. A., Song, J., Lee, J. T. 2008; 322 (5902): 750-756


    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.

    View details for DOI 10.1126/science.1163045

    View details for Web of Science ID 000260605200052

    View details for PubMedID 18974356

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