BRPF3-HBO1 Regulates Replication Origin Activation and Histone H3K14 Acetylation

Overview

Journal EMBO J

Specialties Biotechnology
Molecular Biology

Date 2015 Dec 2

PMID 26620551

Citations 73

Authors

Yunpeng Feng

Arsenios Vlassis

Celine Roques

Marie-Eve Lalonde

Cristina Gonzalez-Aguilera

Jean-Philippe Lambert

Sung-Bau Lee

Xiaobei Zhao

Constance Alabert

Jens V Johansen

Eric Paquet

Xiang-Jiao Yang

Anne-Claude Gingras

Jacques Cote

Anja Groth

Affiliations

Soon will be listed here.

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 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.

Citing Articles

Whole-exome sequencing and Drosophila modelling reveal mutated genes and pathways contributing to human ovarian failure.

Henarejos-Castillo I, Sanz F, Solana-Manrique C, Sebastian-Leon P, Medina I, Remohi J Reprod Biol Endocrinol. 2024; 22(1):153.

PMID: 39633407 PMC: 11616368. DOI: 10.1186/s12958-024-01325-4.

Multifunctional acyltransferase HBO1: a key regulatory factor for cellular functions.

Su Z, Zhang Y, Tang J, Zhou Y, Long C Cell Mol Biol Lett. 2024; 29(1):141.

PMID: 39543485 PMC: 11566351. DOI: 10.1186/s11658-024-00661-y.

KAT6B is required for histone 3 lysine 9 acetylation and SOX gene expression in the developing brain.

Bergamasco M, Abeysekera W, Garnham A, Hu Y, Li-Wai-Suen C, Sheikh B Life Sci Alliance. 2024; 8(2).

PMID: 39537341 PMC: 11561263. DOI: 10.26508/lsa.202402969.

HBO1, a MYSTerious KAT and its links to cancer.

Yokoyama A, Niida H, Kutateladze T, Cote J Biochim Biophys Acta Gene Regul Mech. 2024; 1867(3):195045.

PMID: 38851533 PMC: 11330361. DOI: 10.1016/j.bbagrm.2024.195045.

Integrative analysis of DNA replication origins and ORC-/MCM-binding sites in human cells reveals a lack of overlap.

Tian M, Wang Z, Su Z, Shibata E, Shibata Y, Dutta A Elife. 2024; 12.

PMID: 38567819 PMC: 10990492. DOI: 10.7554/eLife.89548.

References

Iizuka M, Stillman B . Histone acetyltransferase HBO1 interacts with the ORC1 subunit of the human initiator protein. J Biol Chem. 1999; 274(33):23027-34. DOI: 10.1074/jbc.274.33.23027. View

Tardat M, Brustel J, Kirsh O, Lefevbre C, Callanan M, Sardet C . The histone H4 Lys 20 methyltransferase PR-Set7 regulates replication origins in mammalian cells. Nat Cell Biol. 2010; 12(11):1086-93. DOI: 10.1038/ncb2113. View

Gurvich N, Perna F, Farina A, Voza F, Menendez S, Hurwitz J . L3MBTL1 polycomb protein, a candidate tumor suppressor in del(20q12) myeloid disorders, is essential for genome stability. Proc Natl Acad Sci U S A. 2010; 107(52):22552-7. PMC: 3012470. DOI: 10.1073/pnas.1017092108. View

Dellino G, Cittaro D, Piccioni R, Luzi L, Banfi S, Segalla S . Genome-wide mapping of human DNA-replication origins: levels of transcription at ORC1 sites regulate origin selection and replication timing. Genome Res. 2012; 23(1):1-11. PMC: 3530669. DOI: 10.1101/gr.142331.112. View

Feng Y, Vlassis A, Roques C, Lalonde M, Gonzalez-Aguilera C, Lambert J . BRPF3-HBO1 regulates replication origin activation and histone H3K14 acetylation. EMBO J. 2015; 35(2):176-92. PMC: 4718456. DOI: 10.15252/embj.201591293. View

Ibarra A, Schwob E, Mendez J . Excess MCM proteins protect human cells from replicative stress by licensing backup origins of replication. Proc Natl Acad Sci U S A. 2008; 105(26):8956-61. PMC: 2449346. DOI: 10.1073/pnas.0803978105. View

Kusch T, Florens L, MacDonald W, Swanson S, Glaser R, Yates 3rd J . Acetylation by Tip60 is required for selective histone variant exchange at DNA lesions. Science. 2004; 306(5704):2084-7. DOI: 10.1126/science.1103455. View

Unnikrishnan A, Gafken P, Tsukiyama T . Dynamic changes in histone acetylation regulate origins of DNA replication. Nat Struct Mol Biol. 2010; 17(4):430-7. PMC: 3060656. DOI: 10.1038/nsmb.1780. View

Konig R, Chiang C, Tu B, Yan S, DeJesus P, Romero A . A probability-based approach for the analysis of large-scale RNAi screens. Nat Methods. 2007; 4(10):847-9. DOI: 10.1038/nmeth1089. View

10.

Beck D, Burton A, Oda H, Ziegler-Birling C, Torres-Padilla M, Reinberg D . The role of PR-Set7 in replication licensing depends on Suv4-20h. Genes Dev. 2012; 26(23):2580-9. PMC: 3521623. DOI: 10.1101/gad.195636.112. View

11.

Van C, Yan S, Michael W, Waga S, Cimprich K . Continued primer synthesis at stalled replication forks contributes to checkpoint activation. J Cell Biol. 2010; 189(2):233-46. PMC: 2856894. DOI: 10.1083/jcb.200909105. View

12.

Woodward A, Gohler T, Luciani M, Oehlmann M, Ge X, Gartner A . Excess Mcm2-7 license dormant origins of replication that can be used under conditions of replicative stress. J Cell Biol. 2006; 173(5):673-83. PMC: 2063885. DOI: 10.1083/jcb.200602108. View

13.

Lubelsky Y, Prinz J, DeNapoli L, Li Y, Belsky J, MacAlpine D . DNA replication and transcription programs respond to the same chromatin cues. Genome Res. 2014; 24(7):1102-14. PMC: 4079966. DOI: 10.1101/gr.160010.113. View

14.

You L, Yan K, Zou J, Zhou J, Zhao H, Bertos N . The lysine acetyltransferase activator Brpf1 governs dentate gyrus development through neural stem cells and progenitors. PLoS Genet. 2015; 11(3):e1005034. PMC: 4355587. DOI: 10.1371/journal.pgen.1005034. View

15.

Aggarwal B, Calvi B . Chromatin regulates origin activity in Drosophila follicle cells. Nature. 2004; 430(6997):372-6. DOI: 10.1038/nature02694. View

16.

Cimprich K, Cortez D . ATR: an essential regulator of genome integrity. Nat Rev Mol Cell Biol. 2008; 9(8):616-27. PMC: 2663384. DOI: 10.1038/nrm2450. View

17.

Sun Y, Jiang X, Chen S, Fernandes N, Price B . A role for the Tip60 histone acetyltransferase in the acetylation and activation of ATM. Proc Natl Acad Sci U S A. 2005; 102(37):13182-7. PMC: 1197271. DOI: 10.1073/pnas.0504211102. View

18.

Veno S, Kulikowicz T, Pestana C, Stepien P, Stevnsner T, Bohr V . The human Suv3 helicase interacts with replication protein A and flap endonuclease 1 in the nucleus. Biochem J. 2011; 440(2):293-300. PMC: 4366949. DOI: 10.1042/BJ20100991. View

19.

Mejlvang J, Feng Y, Alabert C, Neelsen K, Jasencakova Z, Zhao X . New histone supply regulates replication fork speed and PCNA unloading. J Cell Biol. 2014; 204(1):29-43. PMC: 3882791. DOI: 10.1083/jcb.201305017. View

20.

Besnard E, Babled A, Lapasset L, Milhavet O, Parrinello H, Dantec C . Unraveling cell type-specific and reprogrammable human replication origin signatures associated with G-quadruplex consensus motifs. Nat Struct Mol Biol. 2012; 19(8):837-44. DOI: 10.1038/nsmb.2339. View