Comprehensive Mapping of Histone Modifications at DNA Double-Strand Breaks Deciphers Repair Pathway Chromatin Signatures.
Comprehensive Mapping of Histone Modifications at DNA Double-Strand Breaks Deciphers Repair Pathway Chromatin Signatures.
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DOI：
10.1016/j.molcel.2018.08.020
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发表时间：
2018-10-18
期刊：
影响因子：
16
通讯作者：
Legube G
中科院分区：
文献类型：
--
作者：
Clouaire T;Rocher V;Lashgari A;Arnould C;Aguirrebengoa M;Biernacka A;Skrzypczak M;Aymard F;Fongang B;Dojer N;Iacovoni JS;Rowicka M;Ginalski K;Côté J;Legube G
双链断裂（DSBs）是极其有害的DNA损伤，可导致癌症驱动突变和易位。非同源末端连接（Non-homologous end joining， NHEJ）和同源重组（homologous recombination， HR）是染色质环境下确保基因组稳定性的两种主要修复途径。尽管做了大量的努力，我们对dsb诱导的染色质的了解仍然是碎片化的。在这里，我们使用ChIP-seq描述了在人类基因组中分布的多个dsb上的20个染色质特征的分布。我们提供了最全面的染色质景观的图片设置在dsb和鉴定NHEJ和hr特异性染色质事件。这项研究揭示了dsb诱导的组蛋白H2B赖氨酸120上的单泛素化到乙酰化开关的存在，可能是由SAGA复合物介导的，以及hr修复的dsb上的高阶信号传导，其中组蛋白H1被排除，而泛素和53BP1积聚在整个γH2AX结构域上。通过ChIP-seq H2BK120揭示的DSB-染色质结构和HR/NHEJ染色质特征在局部范围内经历了从泛素化到乙酰化的转换，H1被去除，泛素在整个γ - h2ax结构域上积累，主要在HR DSB 53BP1分布在兆酶大小的结构域上，主要在HR易发的DSB的G1上。Clouaire等人报道了dsb染色质景观的全面视图，并破译了与HR和NHEJ修复相关的染色质特征。
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. 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.
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DOI：
10.1073/pnas.1504868112
发表时间：
2015-06-16
影响因子：
11.1
作者：
Gursoy-Yuzugullu, Ozge;Ayrapetov, Marina K.;Price, Brendan D.
通讯作者：
Price, Brendan D.
影响因子：
48
作者：
Crosetto, Nicola;Mitra, Abhishek;Silva, Maria Joao;Bienko, Magda;Dojer, Norbert;Wang, Qi;Karaca, Elif;Chiarle, Roberto;Skrzypczak, Magdalena;Ginalski, Krzysztof;Pasero, Philippe;Rowicka, Maga;Dikic, Ivan
通讯作者：
Dikic, Ivan
影响因子：
16
作者：
Downs, JA;Allard, S;Côté, J
通讯作者：
Côté, J
影响因子：
25
作者：
Dobbin MM;Madabhushi R;Pan L;Chen Y;Kim D;Gao J;Ahanonu B;Pao PC;Qiu Y;Zhao Y;Tsai LH
通讯作者：
Tsai LH
影响因子：
16.6
作者：
Cohen S;Puget N;Lin YL;Clouaire T;Aguirrebengoa M;Rocher V;Pasero P;Canitrot Y;Legube G
通讯作者：
Legube G