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.
journal_name
Nat Struct Mol Bioljournal_title
Nature structural & molecular biologyauthors
Musselman CA,Avvakumov N,Watanabe R,Abraham CG,Lalonde ME,Hong Z,Allen C,Roy S,Nuñez JK,Nickoloff J,Kulesza CA,Yasui A,Côté J,Kutateladze TGdoi
10.1038/nsmb.2435subject
Has Abstractpub_date
2012-12-01 00:00:00pages
1266-72issue
12eissn
1545-9993issn
1545-9985pii
nsmb.2435journal_volume
19pub_type
杂志文章abstract::Telomere capping conceals chromosome ends from exonucleases and checkpoints, but the full range of capping mechanisms is not well defined. Telomeres have the potential to form G-quadruplex (G4) DNA, although evidence for telomere G4 DNA function in vivo is limited. In budding yeast, capping requires the Cdc13 protein ...
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