title: CHD5, a brain-specific paralog of Mi2 chromatin remodeling enzymes, regulates expression of neuronal genes.
abstract: 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.
authors.affiliation: Laboratory of Molecular Biology and Immunology, National Institute on Aging Intramural Research Program, National Institutes of Health, Baltimore, Maryland, United States of America.
authors.forename: Rebecca Casaday
authors.initials: RC
authors.lastname: Potts
authors.forename: Peisu
authors.initials: P
authors.lastname: Zhang
authors.forename: Andrea L
authors.initials: AL
authors.lastname: Wurster
authors.forename: Patricia
authors.initials: P
authors.lastname: Precht
authors.forename: Mohamed R
authors.initials: MR
authors.lastname: Mughal
authors.forename: William H
authors.initials: WH
authors.lastname: Wood
authors.forename: Yonqing
authors.initials: Y
authors.lastname: Zhang
authors.forename: Kevin G
authors.initials: KG
authors.lastname: Becker
authors.forename: Mark P
authors.initials: MP
authors.lastname: Mattson
authors.forename: Michael J
authors.initials: MJ
authors.lastname: Pazin
mesh_terms: D000375:Aging; D000544:Alzheimer Disease / Q000378:metabolism; D000818:Animals; D001921:Brain / Q000201:enzymology / Q000502:physiology; D002843:Chromatin / Q000737:chemistry*; D047369:Chromatin Immunoprecipitation; D004265:DNA Helicases / Q000096:biosynthesis*; D020869:Gene Expression Profiling; D015971:Gene Expression Regulation, Enzymologic; D006801:Humans; D056245:Mi-2 Nucleosome Remodeling and Deacetylase Complex / Q000096:biosynthesis*; D051379:Mice; D046912:Multiprotein Complexes; D009474:Neurons / Q000378:metabolism*; D020411:Oligonucleotide Array Sequence Analysis; D051381:Rats; D015534:Trans-Activators / Q000096:biosynthesis*
chemical_list: D002843:Chromatin; D046912:Multiprotein Complexes; D015534:Trans-Activators; D056245:Mi-2 Nucleosome Remodeling and Deacetylase Complex; D004265:DNA Helicases; C572553:CHD5 protein, rat; C550983:Chd6 protein, mouse; C511083:Chd9 protein, mouse