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Modulation of chromatin position and gene expression by HDAC4 interaction with nucleoporins
Class IIa histone deacetylases (HDACs) can modulate chromatin architecture and transcriptional activity, thereby participating in the regulation of cellular responses such as cardiomyocyte hypertrophy. However, the target genes of class IIa HDACs that control inducible cardiac growth and the broader...
Autores principales: | , , , |
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Formato: | Texto |
Lenguaje: | English |
Publicado: |
The Rockefeller University Press
2011
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3082185/ https://www.ncbi.nlm.nih.gov/pubmed/21464227 http://dx.doi.org/10.1083/jcb.201101046 |
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author | Kehat, Izhak Accornero, Federica Aronow, Bruce J. Molkentin, Jeffery D. |
author_facet | Kehat, Izhak Accornero, Federica Aronow, Bruce J. Molkentin, Jeffery D. |
author_sort | Kehat, Izhak |
collection | PubMed |
description | Class IIa histone deacetylases (HDACs) can modulate chromatin architecture and transcriptional activity, thereby participating in the regulation of cellular responses such as cardiomyocyte hypertrophy. However, the target genes of class IIa HDACs that control inducible cardiac growth and the broader mechanisms whereby these deacetylases modulate locus-specific gene expression within chromatin remain a mystery. Here, we used genome-wide promoter occupancy analysis, expression profiling, and primary cell validation to identify direct class IIa HDAC4 targets in cardiomyocytes. Simultaneously, we identified nucleoporin155 (Nup155) as an HDAC4-interacting protein. Mechanistically, we show that HDAC4 modulated the association of identified target genes with nucleoporins through interaction with Nup155. Moreover, a truncated mutant of Nup155 that cannot bind HDAC4 suppressed HDAC4-induced gene expression patterns and chromatin–nucleoporin association, suggesting that Nup155-mediated localization was required for HDAC4’s effect on gene expression. We thus propose a novel mechanism of action for HDAC4, suggesting it can function to dynamically regulate gene expression through changes in chromatin–nucleoporin association. |
format | Text |
id | pubmed-3082185 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2011 |
publisher | The Rockefeller University Press |
record_format | MEDLINE/PubMed |
spelling | pubmed-30821852011-10-04 Modulation of chromatin position and gene expression by HDAC4 interaction with nucleoporins Kehat, Izhak Accornero, Federica Aronow, Bruce J. Molkentin, Jeffery D. J Cell Biol Research Articles Class IIa histone deacetylases (HDACs) can modulate chromatin architecture and transcriptional activity, thereby participating in the regulation of cellular responses such as cardiomyocyte hypertrophy. However, the target genes of class IIa HDACs that control inducible cardiac growth and the broader mechanisms whereby these deacetylases modulate locus-specific gene expression within chromatin remain a mystery. Here, we used genome-wide promoter occupancy analysis, expression profiling, and primary cell validation to identify direct class IIa HDAC4 targets in cardiomyocytes. Simultaneously, we identified nucleoporin155 (Nup155) as an HDAC4-interacting protein. Mechanistically, we show that HDAC4 modulated the association of identified target genes with nucleoporins through interaction with Nup155. Moreover, a truncated mutant of Nup155 that cannot bind HDAC4 suppressed HDAC4-induced gene expression patterns and chromatin–nucleoporin association, suggesting that Nup155-mediated localization was required for HDAC4’s effect on gene expression. We thus propose a novel mechanism of action for HDAC4, suggesting it can function to dynamically regulate gene expression through changes in chromatin–nucleoporin association. The Rockefeller University Press 2011-04-04 /pmc/articles/PMC3082185/ /pubmed/21464227 http://dx.doi.org/10.1083/jcb.201101046 Text en © 2011 Kehat et al. This article is distributed under the terms of an Attribution–Noncommercial–Share Alike–No Mirror Sites license for the first six months after the publication date (see http://www.rupress.org/terms). After six months it is available under a Creative Commons License (Attribution–Noncommercial–Share Alike 3.0 Unported license, as described at http://creativecommons.org/licenses/by-nc-sa/3.0/). |
spellingShingle | Research Articles Kehat, Izhak Accornero, Federica Aronow, Bruce J. Molkentin, Jeffery D. Modulation of chromatin position and gene expression by HDAC4 interaction with nucleoporins |
title | Modulation of chromatin position and gene expression by HDAC4 interaction with nucleoporins |
title_full | Modulation of chromatin position and gene expression by HDAC4 interaction with nucleoporins |
title_fullStr | Modulation of chromatin position and gene expression by HDAC4 interaction with nucleoporins |
title_full_unstemmed | Modulation of chromatin position and gene expression by HDAC4 interaction with nucleoporins |
title_short | Modulation of chromatin position and gene expression by HDAC4 interaction with nucleoporins |
title_sort | modulation of chromatin position and gene expression by hdac4 interaction with nucleoporins |
topic | Research Articles |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3082185/ https://www.ncbi.nlm.nih.gov/pubmed/21464227 http://dx.doi.org/10.1083/jcb.201101046 |
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