| Literature DB >> 28486105 |
Limin Xia1, Wenjie Huang2, Marina Bellani3, Michael M Seidman3, Kaichun Wu2, Daiming Fan2, Yongzhan Nie2, Yi Cai4, Yang W Zhang4, Li-Rong Yu5, Huili Li4, Cynthia A Zahnow4, Wenbing Xie4, Ray-Whay Chiu Yen4, Feyruz V Rassool6, Stephen B Baylin7.
Abstract
An oncogenic role for CHD4, a NuRD component, is defined for initiating and supporting tumor suppressor gene (TSG) silencing in human colorectal cancer. CHD4 recruits repressive chromatin proteins to sites of DNA damage repair, including DNA methyltransferases where it imposes de novo DNA methylation. At TSGs, CHD4 retention helps maintain DNA hypermethylation-associated transcriptional silencing. CHD4 is recruited by the excision repair protein OGG1 for oxidative damage to interact with the damage-induced base 8-hydroxydeoxyguanosine (8-OHdG), while ZMYND8 recruits it to double-strand breaks. CHD4 knockdown activates silenced TSGs, revealing their role for blunting colorectal cancer cell proliferation, invasion, and metastases. High CHD4 and 8-OHdG levels plus low expression of TSGs strongly correlates with early disease recurrence and decreased overall survival.Entities:
Keywords: Chromodomain helicase DNA-binding protein 4; DNA methylation; DNA methyltransferase; colorectal cancer; double strand break; histone modification; metastases; nucleosome remodeling and histone deacetylation complex; oxidative damage; tumor suppressor gene
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Year: 2017 PMID： 28486105 PMCID： PMC5587180 DOI： 10.1016/j.ccell.2017.04.005
Source DB: PubMed Journal: Cancer Cell ISSN： 1535-6108 Impact factor: 31.743