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

    Research output: Contribution to journalArticlepeer-review

    114 Citations (Scopus)

    Abstract

    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.

    Original languageEnglish
    Pages (from-to)1266-1272
    Number of pages7
    JournalNature Structural and Molecular Biology
    Volume19
    Issue number12
    DOIs
    Publication statusPublished - 2012 Dec

    ASJC Scopus subject areas

    • Structural Biology
    • Molecular Biology

    Fingerprint Dive into the research topics of 'Molecular basis for H3K36me3 recognition by the Tudor domain of PHF1'. Together they form a unique fingerprint.

    Cite this