@article{14fa76035c1841dcaae72c3e934bb66b,
title = "Comprehensive Mapping of Histone Modifications at DNA Double-Strand Breaks Deciphers Repair Pathway Chromatin Signatures",
abstract = "Double-strand breaks (DSBs) are extremely detrimental DNA lesions that can lead to cancer-driving mutations and translocations. Non-homologous end joining (NHEJ) and homologous recombination (HR) represent the two main repair pathways operating in the context of chromatin to ensure genome stability. Despite extensive efforts, our knowledge of DSB-induced chromatin still remains fragmented. Here, we describe the distribution of 20 chromatin features at multiple DSBs spread throughout the human genome using ChIP-seq. We provide the most comprehensive picture of the chromatin landscape set up at DSBs and identify NHEJ- and HR-specific chromatin events. This study revealed the existence of a DSB-induced monoubiquitination-to-acetylation switch on histone H2B lysine 120, likely mediated by the SAGA complex, as well as higher-order signaling at HR-repaired DSBs whereby histone H1 is evicted while ubiquitin and 53BP1 accumulate over the entire γH2AX domains. Using ChIP-seq in a cell line where multiple annotated DNA double-strand breaks can be induced on the human genome, Clouaire et al. report a comprehensive view of the chromatin landscape set up at DSBs and decipher the chromatin signature associated with HR and NHEJ repair.",
keywords = "53BP1, ChIP-seq, DNA double-strand breaks, DSB repair, chromatin, histone H1, histone modifications, homologous recombination, non-homologous end joining, γH2AX",
author = "Thomas Clouaire and Vincent Rocher and Anahita Lashgari and Coline Arnould and Marion Aguirrebengoa and Anna Biernacka and Magdalena Skrzypczak and Fran{\c c}ois Aymard and Bernard Fongang and Norbert Dojer and Iacovoni, {Jason S.} and Maga Rowicka and Krzysztof Ginalski and Jacques C{\^o}t{\'e} and Ga{\"e}lle Legube",
note = "Funding Information: We thank the GeneCore facility of EMBL for high-throughput sequencing. We thank K.M. Miller (University of Texas) for critical reading of the manuscript and J.-Y. Masson/G. Dellaire for reagents and advice for the Clover/HR assay. Funding was provided by Polish National Science Centre ( 2011/02/A/NZ2/00014 to K.G., 2016/21/B/ST6/01471 to N.D., and 2015/17/D/NZ2/03711 to M.S.) and Foundation for Polish Science ( TEAM to K.G.). Funding to M.R., B.F., and N.D. was provided by NIH ( 5 R01 GM 112131 ). J.C. acknowledges funding support from the Canadian Institutes of Health Research ( FND-143314 ) and holds the Canada Research Chair in Chromatin Biology and Molecular Epigenetics. M.A. was supported by the Fondation pour la Recherche M{\'e}dicale (FRM). Funding in G.L.{\textquoteright}s laboratory was provided by grants from the European Research Council ( ERC-2014-CoG 647344 ), Agence Nationale pour la Recherche ( ANR-14-CE10-0002-01 and ANR-13-BSV8-0013 ), the Institut National contre le Cancer (INCA), and the Ligue Nationale contre le Cancer (LNCC). T.C. is an INSERM researcher. Funding Information: We thank the GeneCore facility of EMBL for high-throughput sequencing. We thank K.M. Miller (University of Texas) for critical reading of the manuscript and J.-Y. Masson/G. Dellaire for reagents and advice for the Clover/HR assay. Funding was provided by Polish National Science Centre (2011/02/A/NZ2/00014 to K.G., 2016/21/B/ST6/01471 to N.D., and 2015/17/D/NZ2/03711 to M.S.) and Foundation for Polish Science (TEAM to K.G.). Funding to M.R., B.F., and N.D. was provided by NIH (5 R01 GM 112131). J.C. acknowledges funding support from the Canadian Institutes of Health Research (FND-143314) and holds the Canada Research Chair in Chromatin Biology and Molecular Epigenetics. M.A. was supported by the Fondation pour la Recherche M{\'e}dicale (FRM). Funding in G.L.'s laboratory was provided by grants from the European Research Council (ERC-2014-CoG 647344), Agence Nationale pour la Recherche (ANR-14-CE10-0002-01 and ANR-13-BSV8-0013), the Institut National contre le Cancer (INCA), and the Ligue Nationale contre le Cancer (LNCC). T.C. is an INSERM researcher.",
year = "2018",
month = oct,
day = "18",
doi = "10.1016/j.molcel.2018.08.020",
language = "English (US)",
volume = "72",
pages = "250--262.e6",
journal = "Molecular Cell",
issn = "1097-2765",
publisher = "Cell Press",
number = "2",
}