Comprehensive Mapping of Histone Modifications at DNA Double-Strand Breaks Deciphers Repair Pathway Chromatin Signatures

• Published in: Molecular cell Vol. 72; no. 2; pp. 250 - 262.e6
• Main Authors: Clouaire, Thomas, Rocher, Vincent, Lashgari, Anahita, Arnould, Coline, Aguirrebengoa, Marion, Biernacka, Anna, Skrzypczak, Magdalena, Aymard, François, Fongang, Bernard, Dojer, Norbert, Iacovoni, Jason S., Rowicka, Maga, Ginalski, Krzysztof, Côté, Jacques, Legube, Gaëlle
• Format: Journal Article
• Language: English
• Published: United States Elsevier Inc 18-10-2018; Cell Press
• Subjects: 53BP1; Biochemistry, Molecular Biology; Cell Line, Tumor; ChIP-seq; chromatin; Chromatin - genetics; DNA Breaks, Double-Stranded; DNA double-strand breaks; DNA Repair - genetics; DSB repair; Genomic Instability - genetics; histone H1; histone modifications; Histones - genetics; homologous recombination; Homologous Recombination - genetics; Humans; K562 Cells; Life Sciences; Molecular biology; non-homologous end joining; Tumor Suppressor p53-Binding Protein 1 - genetics; γH2AX; histone H1; homologous recombination; 53BP1; γH2AX; ChIP-seq; DSB repair; non-homologous end joining; histone modifications; DNA double-strand breaks; chromatin
• ISSN: 1097-2765; 1097-4164
• DOI: 10.1016/j.molcel.2018.08.020

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.
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•DSB-chromatin landscape and HR/NHEJ chromatin signatures uncovered by ChIP-seq•H2BK120 undergoes a switch from ubiquitination to acetylation at a local scale•H1 is removed and ubiquitin accumulates on entire γH2AX domains, mainly at HR DSB•53BP1 spreads over megabase-sized domains, mostly in G1 at HR-prone DSBs
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.