@article{c14f86c7b20c410f9d0225e0e96595a7,
title = "EGFR Modulates DNA Synthesis and Repair through Tyr Phosphorylation of Histone H4",
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.",
author = "Chou, {Ruey Hwang} and Wang, {Ying Nai} and Hsieh, {Yi Hsien} and Li, {Long Yuan} and Weiya Xia and Chang, {Wei Chao} and Chang, {Ling Chu} and Cheng, {Chien Chia} and Lai, {Chien Chen} and Hsu, {Jennifer L.} and Chang, {Wei Jung} and Chiang, {Shu Ya} and Lee, {Hong Jen} and Liao, {Hsin Wei} and Chuang, {Pei Huan} and Chen, {Hui Yu} and Wang, {Hung Ling} and Kuo, {Sheng Chu} and Chen, {Chung Hsuan} and Yu, {Yung Luen} and Hung, {Mien Chie}",
note = "Funding Information: We thank the National RNAi Core Facility (Academia Sinica, Taipei, Taiwan) for providing the shRNAs. We appreciate Dr. Stephanie A. Miller (Department of Molecular and Cellular Oncology) and Dr. Tamara Locke (Scientific Publications) at The University of Texas MD Anderson Cancer Center for their assistance in editing the manuscript and Jung-Mao Hsu for drawing the proposed model. This research is supported in part by the National Institutes of Health (Cancer Center Support Grants CA016672, CA109311, and CA099031), The University of Texas MD Anderson Cancer Center–China Medical University and Hospital Sister Institution Fund, and the following grants from Taiwan: NSC99-2320-B-039-030-MY3, NSC102-2321-B-039-004, NHRI-EX102-10245BI (to Y.-L.Y.); NHRI-EX98-9603BC (to L.-Y.L.); MOHW103-TD-B-111-03 (to L.-Y.L., Y.-L.Y., and M.-C.H.); NSC2321-B-039 and NSC99-2632-B-039-001-MY3 (to M.-C.H., Y.-L.Y., and L.-Y.L.); NSC 103-2911-I-002-303 (to M.-C.H. and W-C.C.); and NSC101-2311-B-039-001, CMU100-N2-09, and CMU101-N2-04 (to R.-H.C.). This work is in memoriam of Mr. Tiong Loi Ang for his courageous fight against cancer. ",
year = "2014",
month = jul,
day = "28",
doi = "10.1016/j.devcel.2014.06.008",
language = "English (US)",
volume = "30",
pages = "224--237",
journal = "Developmental cell",
issn = "1534-5807",
publisher = "Cell Press",
number = "2",
}