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    Please use this identifier to cite or link to this item: http://asiair.asia.edu.tw/ir/handle/310904400/86907


    Title: EGFR modulates DNA synthesis and repair through Tyr phosphorylation of histone H4
    Authors: 鄒瑞煌;Wang, YN;Wang, YN;Hsieh, YH;Hsieh, YH;李龍緣;Xia, W;Xia, W;Chang, WC;Chang, WC;Chang, LC;Chang, LC;Cheng, CC;Cheng, CC;Chang, WJ;Chang, WJ;Chiang, SY;Chiang, SY;Lee, HJ;Lee, HJ;Liao, HW;Liao, HW
    Contributors: 生物科技學系
    Date: 2014-07
    Issue Date: 2014-11-07 14:48:21 (UTC+8)
    Abstract: Posttranslational modifications of histones play fundamental roles in many biological functions. Specifically, histone H4-K20 methylation is critical for 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 monomethylation, and the Ki-67 proliferation marker. These findings uncover a mechanism by which EGFR transduces signal to chromatin to regulate DNA synthesis and repair.
    Relation: DEVELOPMENTAL CELL,30(2),224–237.
    Appears in Collections:[生物科技學系] 期刊論文

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