[PDF][PDF] CHD4 has oncogenic functions in initiating and maintaining epigenetic suppression of multiple tumor suppressor genes

L Xia, W Huang, M Bellani, MM Seidman, K Wu, D Fan… - Cancer cell, 2017 - cell.com
L Xia, W Huang, M Bellani, MM Seidman, K Wu, D Fan, Y Nie, Y Cai, YW Zhang, LR Yu, H Li…
Cancer cell, 2017cell.com
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 …
Summary
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.
cell.com