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

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 p...

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Autores principales: Rebecca Casaday Potts, Peisu Zhang, Andrea L Wurster, Patricia Precht, Mohamed R Mughal, William H Wood, Yonqing Zhang, Kevin G Becker, Mark P Mattson, Michael J Pazin
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Publicado: Public Library of Science (PLoS) 2011
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spelling oai:doaj.org-article:b6dc22d1f8ee429592a18734217617792021-11-04T06:08:44ZCHD5, a brain-specific paralog of Mi2 chromatin remodeling enzymes, regulates expression of neuronal genes.1932-620310.1371/journal.pone.0024515https://doaj.org/article/b6dc22d1f8ee429592a18734217617792011-01-01T00:00:00Zhttps://www.ncbi.nlm.nih.gov/pmc/articles/pmid/21931736/?tool=EBIhttps://doaj.org/toc/1932-6203CHD5 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.Rebecca Casaday PottsPeisu ZhangAndrea L WursterPatricia PrechtMohamed R MughalWilliam H WoodYonqing ZhangKevin G BeckerMark P MattsonMichael J PazinPublic Library of Science (PLoS)articleMedicineRScienceQENPLoS ONE, Vol 6, Iss 9, p e24515 (2011)
institution DOAJ
collection DOAJ
language EN
topic Medicine
R
Science
Q
spellingShingle Medicine
R
Science
Q
Rebecca Casaday Potts
Peisu Zhang
Andrea L Wurster
Patricia Precht
Mohamed R Mughal
William H Wood
Yonqing Zhang
Kevin G Becker
Mark P Mattson
Michael J Pazin
CHD5, a brain-specific paralog of Mi2 chromatin remodeling enzymes, regulates expression of neuronal genes.
description 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.
format article
author Rebecca Casaday Potts
Peisu Zhang
Andrea L Wurster
Patricia Precht
Mohamed R Mughal
William H Wood
Yonqing Zhang
Kevin G Becker
Mark P Mattson
Michael J Pazin
author_facet Rebecca Casaday Potts
Peisu Zhang
Andrea L Wurster
Patricia Precht
Mohamed R Mughal
William H Wood
Yonqing Zhang
Kevin G Becker
Mark P Mattson
Michael J Pazin
author_sort Rebecca Casaday Potts
title CHD5, a brain-specific paralog of Mi2 chromatin remodeling enzymes, regulates expression of neuronal genes.
title_short CHD5, a brain-specific paralog of Mi2 chromatin remodeling enzymes, regulates expression of neuronal genes.
title_full CHD5, a brain-specific paralog of Mi2 chromatin remodeling enzymes, regulates expression of neuronal genes.
title_fullStr CHD5, a brain-specific paralog of Mi2 chromatin remodeling enzymes, regulates expression of neuronal genes.
title_full_unstemmed CHD5, a brain-specific paralog of Mi2 chromatin remodeling enzymes, regulates expression of neuronal genes.
title_sort chd5, a brain-specific paralog of mi2 chromatin remodeling enzymes, regulates expression of neuronal genes.
publisher Public Library of Science (PLoS)
publishDate 2011
url https://doaj.org/article/b6dc22d1f8ee429592a1873421761779
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