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.

中文翻译：

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CHD4在启动和维持多种肿瘤抑制基因的表观遗传抑制中具有致癌作用

定义了NuRD组分CHD4的致癌作用，用于启动和支持人类结直肠癌中的肿瘤抑制基因（TSG）沉默。CHD4将抑制性染色质蛋白募集到DNA损伤修复位点，包括在其中施加从头DNA甲基化的DNA甲基转移酶。在TSG处，CHD4保留有助于维持DNA超甲基化相关的转录沉默。CHD4由切除修复蛋白OGG1募集，用于氧化性损伤，使其与损伤诱导的碱基8-羟基脱氧鸟苷（8-OHdG）相互作用，而ZMYND8则将其募集至双链断裂。CHD4敲低激活沉默的TSG，揭示它们在抑制大肠癌细胞增殖，侵袭和转移中的作用。