CHD4 Has Oncogenic Functions in Initiating and Maintaining Epigenetic Suppression of Multiple Tumor Suppressor Genes.
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.
Mesh Terms:
Animals, Autoantigens, Cell Movement, Cell Proliferation, Clustered Regularly Interspaced Short Palindromic Repeats, Colorectal Neoplasms, DNA (Cytosine-5-)-Methyltransferases, DNA Damage, DNA Glycosylases, DNA Methylation, Deoxyguanosine, Disease-Free Survival, Down-Regulation, Enhancer of Zeste Homolog 2 Protein, Epigenetic Repression, Gene Expression Regulation, Neoplastic, Gene Silencing, Genes, Tumor Suppressor, HCT116 Cells, Histocompatibility Antigens, Histone-Lysine N-Methyltransferase, Humans, Kaplan-Meier Estimate, Mi-2 Nucleosome Remodeling and Deacetylase Complex, Mice, Inbred BALB C, Mice, Nude, Neoplasm Metastasis, Oxidative Stress, Proportional Hazards Models, RNA Interference, Receptors for Activated C Kinase, Receptors, Cell Surface, Time Factors, Transcription, Genetic, Transfection, Tumor Suppressor Proteins
Animals, Autoantigens, Cell Movement, Cell Proliferation, Clustered Regularly Interspaced Short Palindromic Repeats, Colorectal Neoplasms, DNA (Cytosine-5-)-Methyltransferases, DNA Damage, DNA Glycosylases, DNA Methylation, Deoxyguanosine, Disease-Free Survival, Down-Regulation, Enhancer of Zeste Homolog 2 Protein, Epigenetic Repression, Gene Expression Regulation, Neoplastic, Gene Silencing, Genes, Tumor Suppressor, HCT116 Cells, Histocompatibility Antigens, Histone-Lysine N-Methyltransferase, Humans, Kaplan-Meier Estimate, Mi-2 Nucleosome Remodeling and Deacetylase Complex, Mice, Inbred BALB C, Mice, Nude, Neoplasm Metastasis, Oxidative Stress, Proportional Hazards Models, RNA Interference, Receptors for Activated C Kinase, Receptors, Cell Surface, Time Factors, Transcription, Genetic, Transfection, Tumor Suppressor Proteins
Cancer Cell
Date: Dec. 08, 2016
PubMed ID: 28486105
View in: Pubmed Google Scholar
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