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BRPF 3‐ HBO 1 regulates replication origin activation and histone H3K14 acetylation
Author(s) -
Feng Yunpeng,
Vlassis Arsenios,
Roques Céline,
Lalonde MarieEve,
GonzálezAguilera Cristina,
Lambert JeanPhilippe,
Lee SungBau,
Zhao Xiaobei,
Alabert Constance,
Johansen Jens V,
Paquet Eric,
Yang XiangJiao,
Gingras AnneClaude,
Côté Jacques,
Groth Anja
Publication year - 2015
Publication title -
the embo journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 7.484
H-Index - 392
eISSN - 1460-2075
pISSN - 0261-4189
DOI - 10.15252/embj.201591293
Subject(s) - biology , acetylation , histone , microbiology and biotechnology , replication (statistics) , genetics , gene , virology
Abstract During DNA replication, thousands of replication origins are activated across the genome. Chromatin architecture contributes to origin specification and usage, yet it remains unclear which chromatin features impact on DNA replication. Here, we perform a RNA i screen for chromatin regulators implicated in replication control by measuring RPA accumulation upon replication stress. We identify six factors required for normal rates of DNA replication and characterize a function of the bromodomain and PHD finger‐containing protein 3 ( BRPF 3) in replication initiation. BRPF 3 forms a complex with HBO 1 that specifically acetylates histone H3K14, and genomewide analysis shows high enrichment of BRPF 3, HBO 1 and H3K14ac at ORC 1‐binding sites and replication origins found in the vicinity of TSS s. Consistent with this, BRPF 3 is necessary for H3K14ac at selected origins and efficient origin activation. CDC 45 recruitment, but not MCM 2‐7 loading, is impaired in BRPF 3‐depleted cells, identifying a BRPF 3‐dependent function of HBO 1 in origin activation that is complementary to its role in licencing. We thus propose that BRPF 3‐ HBO 1 acetylation of histone H3K14 around TSS facilitates efficient activation of nearby replication origins.