EGFR modulates DNA synthesis and repair through Tyr phosphorylation of histone H4.
EGFR modulates DNA synthesis and repair through Tyr phosphorylation of histone H4.
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DOI：
10.1016/j.devcel.2014.06.008
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发表时间：
2014-07-28
影响因子：
11.8
通讯作者：
Hung, Mien-Chie
中科院分区：
文献类型：
--
作者：
Chou, Ruey-Hwang;Wang, Ying-Nai;Hsieh, Yi-Hsien;Li, Long-Yuan;Xia, Weiya;Chang, Wei-Chao;Chang, Ling-Chu;Cheng, Chien-Chia;Lai, Chien-Chen;Hsu, Jennifer L.;Chang, Wei-Jung;Chiang, Shu-Ya;Lee, Hong-Jen;Liao, Hsin-Wei;Chuang, Pei-Huan;Chen, Hui-Yu;Wang, Hung-Ling;Kuo, Sheng-Chu;Chen, Chung-Hsuan;Yu, Yung-Luen;Hung, Mien-Chie
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Posttranslational modifications of histones play fundamental roles in many biological functions. Specifically, histone H4-K20 methylation is critical in DNA synthesis and repair. However, little is known about how these functions are regulated by the upstream stimuli. Here, we identify a tyrosine phosphorylation site at Y72 of histone H4, which facilitates recruitment of histone methyltransferases (HMTases), SET8 and SUV4-20H, to enhance its K20 methylation, thereby promoting DNA synthesis and repair. Phosphorylation-defective histone H4 mutant is deficient in K20 methylation, leading to reduced DNA synthesis, delayed cell cycle progression, and decreased DNA repair ability. Disrupting the interaction between epidermal growth factor receptor (EGFR) and histone H4 by Y72 peptide significantly reduced tumor growth. Furthermore, EGFR expression clinically correlates with histone H4-Y72 phosphorylation, H4-K20 mono-methylation, and the Ki-67 proliferation marker. These findings uncover a mechanism by which EGFR transduces signal to chromatin to regulate DNA synthesis and repair.
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影响因子：
16
作者：
Oda H;Hübner MR;Beck DB;Vermeulen M;Hurwitz J;Spector DL;Reinberg D
通讯作者：
Reinberg D
影响因子：
16.8
作者：
Mahajan K;Fang B;Koomen JM;Mahajan NP
通讯作者：
Mahajan NP
影响因子：
9.2
作者：
Peterson, CL;Laniel, MA
通讯作者：
Laniel, MA
DOI：
10.1083/jcb.200706150
发表时间：
2007-12-31
期刊：
The Journal of cell biology
影响因子：
--
作者：
Jørgensen S;Elvers I;Trelle MB;Menzel T;Eskildsen M;Jensen ON;Helleday T;Helin K;Sørensen CS
通讯作者：
Sørensen CS
影响因子：
4.8
作者：
Chen, HC;Appeddu, PA;Guan, JL
通讯作者：
Guan, JL