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BRPF3-HBO1 regulates replication origin activation and histone H3K14 acetylation

Publikation: Bidrag til tidsskriftTidsskriftartikelForskningfagfællebedømt

  • Yunpeng Feng
  • Arsenios Vlassis
  • Céline Roques
  • Marie Eve Lalonde
  • Cristina Gonzalez Aguilera
  • Jean Philippe Lambert
  • Sung-Bau Lee
  • Xiaobei Zhao
  • Constance Alabert
  • Johansen, Jens Vilstrup
  • Eric Paquet
  • Xiang Jiao Yang
  • Anne Claude Gingras
  • Jacques Côté
  • Groth, Anja

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 RNAi 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 (BRPF3) in replication initiation. BRPF3 forms a complex with HBO1 that specifically acetylates histone H3K14, and genomewide analysis shows high enrichment of BRPF3, HBO1 and H3K14ac at ORC1-binding sites and replication origins found in the vicinity of TSSs. Consistent with this, BRPF3 is necessary for H3K14ac at selected origins and efficient origin activation. CDC45 recruitment, but not MCM2-7 loading, is impaired in BRPF3-depleted cells, identifying a BRPF3-dependent function of HBO1 in origin activation that is complementary to its role in licencing. We thus propose that BRPF3-HBO1 acetylation of histone H3K14 around TSS facilitates efficient activation of nearby replication origins.

OriginalsprogEngelsk
TidsskriftEMBO Journal
Vol/bind35
Udgave nummer2
Sider (fra-til)176-192
Antal sider17
ISSN0261-4189
DOI
StatusUdgivet - 2016

ID: 153413621