Molecular basis for H3K36me3 recognition by the Tudor domain of PHF1

Catherine A. Musselman, Nikita Avvakumov, Reiko Watanabe, Christopher G. Abraham, Marie Eve Lalonde, Zehui Hong, Christopher Allen, Siddhartha Roy, James K. Nuñez, Jac Nickoloff, Caroline A. Kulesza, Akira Yasui, Jacques Côté, Tatiana G. Kutateladze

    研究成果: Article査読

    124 被引用数 (Scopus)

    抄録

    The PHD finger protein 1 (PHF1) is essential in epigenetic regulation and genome maintenance. Here we show that the Tudor domain of human PHF1 binds to histone H3 trimethylated at Lys36 (H3K36me3). We report a 1.9-Å resolution crystal structure of the Tudor domain in complex with H3K36me3 and describe the molecular mechanism of H3K36me3 recognition using NMR. Binding of PHF1 to H3K36me3 inhibits the ability of the Polycomb PRC2 complex to methylate Lys27 of histone H3 in vitro and in vivo. Laser microirradiation data show that PHF1 is transiently recruited to DNA double-strand breaks, and PHF1 mutants impaired in the H3K36me3 interaction exhibit reduced retention at double-strand break sites. Together, our findings suggest that PHF1 can mediate deposition of the repressive H3K27me3 mark and acts as a cofactor in early DNA-damage response.

    本文言語English
    ページ(範囲)1266-1272
    ページ数7
    ジャーナルNature Structural and Molecular Biology
    19
    12
    DOI
    出版ステータスPublished - 2012 12

    ASJC Scopus subject areas

    • 構造生物学
    • 分子生物学

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