CHD4 Has Oncogenic Functions in Initiating and Maintaining Epigenetic Suppression of Multiple Tumor Suppressor Genes

Limin Xia; Wenjie Huang; Marina Bellani; Michael M. Seidman; Kaichun Wu; Daiming Fan; Yongzhan Nie; Yi Cai; Yang W. Zhang; Li Rong Yu; Huili Li; Cynthia A. Zahnow; Wenbing Xie; Ray Whay Chiu Yen; Feyruz V. Rassool; Stephen B. Baylin

doi:10.1016/j.ccell.2017.04.005

CHD4 Has Oncogenic Functions in Initiating and Maintaining Epigenetic Suppression of Multiple Tumor Suppressor Genes

Limin Xia, Wenjie Huang, Marina Bellani, Michael M. Seidman, Kaichun Wu, Daiming Fan, Yongzhan Nie, Yi Cai, Yang W. Zhang, Li Rong Yu, Huili Li, Cynthia A. Zahnow, Wenbing Xie, Ray Whay Chiu Yen, Feyruz V. Rassool, Stephen B. Baylin

School of Medicine

Research output: Contribution to journal › Article › peer-review

66 Scopus citations

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.

Original language	English (US)
Pages (from-to)	653-668.e7
Journal	Cancer cell
Volume	31
Issue number	5
DOIs	https://doi.org/10.1016/j.ccell.2017.04.005
State	Published - May 8 2017

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

ASJC Scopus subject areas

Oncology
Cancer Research

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10.1016/j.ccell.2017.04.005

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Xia, L., Huang, W., Bellani, M., Seidman, M. M., Wu, K., Fan, D., Nie, Y., Cai, Y., Zhang, Y. W., Yu, L. R., Li, H., Zahnow, C. A., Xie, W., Chiu Yen, R. W., Rassool, F. V., & Baylin, S. B. (2017). CHD4 Has Oncogenic Functions in Initiating and Maintaining Epigenetic Suppression of Multiple Tumor Suppressor Genes. Cancer cell, 31(5), 653-668.e7. https://doi.org/10.1016/j.ccell.2017.04.005

Xia, L, Huang, W, Bellani, M, Seidman, MM, Wu, K, Fan, D, Nie, Y, Cai, Y, Zhang, YW, Yu, LR, Li, H, Zahnow, CA, Xie, W, Chiu Yen, RW, Rassool, FV & Baylin, SB 2017, 'CHD4 Has Oncogenic Functions in Initiating and Maintaining Epigenetic Suppression of Multiple Tumor Suppressor Genes', Cancer cell, vol. 31, no. 5, pp. 653-668.e7. https://doi.org/10.1016/j.ccell.2017.04.005

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title = "CHD4 Has Oncogenic Functions in Initiating and Maintaining Epigenetic Suppression of Multiple Tumor Suppressor Genes",

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.",

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",

author = "Limin Xia and Wenjie Huang and Marina Bellani and Seidman, {Michael M.} and Kaichun Wu and Daiming Fan and Yongzhan Nie and Yi Cai and Zhang, {Yang W.} and Yu, {Li Rong} and Huili Li and Zahnow, {Cynthia A.} and Wenbing Xie and {Chiu Yen}, {Ray Whay} and Rassool, {Feyruz V.} and Baylin, {Stephen B.}",

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year = "2017",

month = may,

day = "8",

doi = "10.1016/j.ccell.2017.04.005",

language = "English (US)",

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AU - Xia, Limin

AU - Huang, Wenjie

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AU - Seidman, Michael M.

AU - Wu, Kaichun

AU - Fan, Daiming

AU - Nie, Yongzhan

AU - Cai, Yi

AU - Zhang, Yang W.

AU - Yu, Li Rong

AU - Li, Huili

AU - Zahnow, Cynthia A.

AU - Xie, Wenbing

AU - Chiu Yen, Ray Whay

AU - Rassool, Feyruz V.

AU - Baylin, Stephen B.

PY - 2017/5/8

Y1 - 2017/5/8

N2 - 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.

AB - 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.

KW - Chromodomain helicase DNA-binding protein 4

KW - DNA methylation

KW - DNA methyltransferase

KW - colorectal cancer

KW - double strand break

KW - histone modification

KW - metastases

KW - nucleosome remodeling and histone deacetylation complex

KW - oxidative damage

KW - tumor suppressor gene

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CHD4 Has Oncogenic Functions in Initiating and Maintaining Epigenetic Suppression of Multiple Tumor Suppressor Genes

Abstract

Keywords

ASJC Scopus subject areas

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