title: Molecular basis for H3K36me3 recognition by the Tudor domain of PHF1.
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.
authors.affiliation: Department of Pharmacology, University of Colorado School of Medicine, Aurora, Colorado, USA.
authors.forename: Catherine A
authors.initials: CA
authors.lastname: Musselman
authors.forename: Nikita
authors.initials: N
authors.lastname: Avvakumov
authors.forename: Reiko
authors.initials: R
authors.lastname: Watanabe
authors.forename: Christopher G
authors.initials: CG
authors.lastname: Abraham
authors.forename: Marie-Eve
authors.initials: ME
authors.lastname: Lalonde
authors.forename: Zehui
authors.initials: Z
authors.lastname: Hong
authors.forename: Christopher
authors.initials: C
authors.lastname: Allen
authors.forename: Siddhartha
authors.initials: S
authors.lastname: Roy
authors.forename: James K
authors.initials: JK
authors.lastname: Nuñez
authors.forename: Jac
authors.initials: J
authors.lastname: Nickoloff
authors.forename: Caroline A
authors.initials: CA
authors.lastname: Kulesza
authors.forename: Akira
authors.initials: A
authors.lastname: Yasui
authors.forename: Jacques
authors.initials: J
authors.lastname: Côté
authors.forename: Tatiana G
authors.initials: TG
authors.lastname: Kutateladze
mesh_terms: D000595:Amino Acid Sequence; D004268:DNA-Binding Proteins / Q000737:chemistry / Q000378:metabolism*; D006657:Histones / Q000378:metabolism*; D006801:Humans; D008958:Models, Molecular; D008969:Molecular Sequence Data; D063146:Polycomb-Group Proteins; D017386:Sequence Homology, Amino Acid; D014157:Transcription Factors / Q000737:chemistry / Q000378:metabolism*
chemical_list: D004268:DNA-Binding Proteins; D006657:Histones; C112309:PHF1 protein, human; D063146:Polycomb-Group Proteins; D014157:Transcription Factors