CHD5, a brain-specific paralog of Mi2 chromatin remodeling enzymes, regulates expression of neuronal genes

• Published in: PloS one Vol. 6; no. 9; p. e24515
• Main Authors: Potts, Rebecca Casaday, Zhang, Peisu, Wurster, Andrea L, Precht, Patricia, Mughal, Mohamed R, Wood, 3rd, William H, Zhang, Yonqing, Becker, Kevin G, Mattson, Mark P, Pazin, Michael J
• Format: Journal Article
• Language: English
• Published: United States Public Library of Science 13-09-2011; Public Library of Science (PLoS)
• Subjects: Adapter proteins; Aging; Alzheimer Disease - metabolism; Alzheimer's disease; Analysis; Animals; ATPases; Biology; Brain; Brain - enzymology; Brain - physiology; Brain research; Cell culture; Cell cycle; Chromatin; Chromatin - chemistry; Chromatin Immunoprecipitation; Chromatin remodeling; Deoxyribonucleic acid; Depletion; DNA; DNA binding proteins; DNA damage; DNA Helicases - biosynthesis; DNA microarrays; Gene expression; Gene Expression Profiling; Gene Expression Regulation, Enzymologic; Gene regulation; Genes; Genomes; HDAC2 protein; Histone deacetylase; Homology; Humans; Immunology; Immunoprecipitation; Laboratories; Mi-2 Nucleosome Remodeling and Deacetylase Complex - biosynthesis; Mice; Molecular biology; Multiprotein Complexes; Mutation; Neuroblastoma; Neurodegenerative diseases; Neurons; Neurons - metabolism; Neurosciences; Oligonucleotide Array Sequence Analysis; Rats; RNA; Trans-Activators - biosynthesis; Transcription (Genetics); Transcription factors; Tumor suppressor genes; United States > US; Maryland; Baltimore Maryland
• ISSN: 1932-6203; 1932-6203
• DOI: 10.1371/journal.pone.0024515

CHD5 is frequently deleted in neuroblastoma and is a tumor suppressor gene. However, little is known about the role of CHD5 other than it is homologous to chromatin remodeling ATPases. We found CHD5 mRNA was restricted to the brain; by contrast, most remodeling ATPases were broadly expressed. CHD5 protein isolated from mouse brain was associated with HDAC2, p66ß, MTA3 and RbAp46 in a megadalton complex. CHD5 protein was detected in several rat brain regions and appeared to be enriched in neurons. CHD5 protein was predominantly nuclear in primary rat neurons and brain sections. Microarray analysis revealed genes that were upregulated and downregulated when CHD5 was depleted from primary neurons. CHD5 depletion altered expression of neuronal genes, transcription factors, and brain-specific subunits of the SWI/SNF remodeling enzyme. Expression of gene sets linked to aging and Alzheimer's disease were strongly altered by CHD5 depletion from primary neurons. Chromatin immunoprecipitation revealed CHD5 bound to these genes, suggesting the regulation was direct. Together, these results indicate that CHD5 protein is found in a NuRD-like multi-protein complex. CHD5 expression is restricted to the brain, unlike the closely related family members CHD3 and CHD4. CHD5 regulates expression of neuronal genes, cell cycle genes and remodeling genes. CHD5 is linked to regulation of genes implicated in aging and Alzheimer's disease.