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Negative Elongation Factor Controls Energy Homeostasis in Cardiomyocytes
Negative elongation factor (NELF) is known to enforce promoter-proximal pausing of RNA polymerase II (Pol II), a pervasive phenomenon observed across multicellular genomes. However, the physiological impact of NELF on tissue homeostasis remains unclear. Here, we show that whole-body conditional dele...
Autores principales: | , , , , , , , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
2014
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4277258/ https://www.ncbi.nlm.nih.gov/pubmed/24656816 http://dx.doi.org/10.1016/j.celrep.2014.02.028 |
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author | Pan, Haihui Qin, Kunhua Guo, Zhanyong Ma, Yonggang April, Craig Gao, Xiaoli Andrews, Thomas G. Bokov, Alex Zhang, Jianhua Chen, Yidong Weintraub, Susan T. Fan, Jian-Bing Wang, Degeng Hu, Yanfen Aune, Gregory J. Lindsey, Merry L. Li, Rong |
author_facet | Pan, Haihui Qin, Kunhua Guo, Zhanyong Ma, Yonggang April, Craig Gao, Xiaoli Andrews, Thomas G. Bokov, Alex Zhang, Jianhua Chen, Yidong Weintraub, Susan T. Fan, Jian-Bing Wang, Degeng Hu, Yanfen Aune, Gregory J. Lindsey, Merry L. Li, Rong |
author_sort | Pan, Haihui |
collection | PubMed |
description | Negative elongation factor (NELF) is known to enforce promoter-proximal pausing of RNA polymerase II (Pol II), a pervasive phenomenon observed across multicellular genomes. However, the physiological impact of NELF on tissue homeostasis remains unclear. Here, we show that whole-body conditional deletion of the B subunit of NELF (NELF-B) in adult mice results in cardiomyopathy and impaired response to cardiac stress. Tissue-specific knockout of NELF-B confirms its cell-autonomous function in cardiomyocytes. NELF directly supports transcription of those genes encoding rate-limiting enzymes in fatty acid oxidation (FAO) and the tricarboxylic acid (TCA) cycle. NELF also shares extensively transcriptional target genes with peroxisome proliferator-activated receptor α (PPARα), a master regulator of energy metabolism in the myocardium. Mechanistically, NELF helps stabilize the transcription initiation complex at the metabolism-related genes. Our findings strongly indicate that NELF is part of the PPARα-mediated transcription regulatory network that maintains metabolic homeostasis in cardiomyocytes. |
format | Online Article Text |
id | pubmed-4277258 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2014 |
record_format | MEDLINE/PubMed |
spelling | pubmed-42772582014-12-26 Negative Elongation Factor Controls Energy Homeostasis in Cardiomyocytes Pan, Haihui Qin, Kunhua Guo, Zhanyong Ma, Yonggang April, Craig Gao, Xiaoli Andrews, Thomas G. Bokov, Alex Zhang, Jianhua Chen, Yidong Weintraub, Susan T. Fan, Jian-Bing Wang, Degeng Hu, Yanfen Aune, Gregory J. Lindsey, Merry L. Li, Rong Cell Rep Article Negative elongation factor (NELF) is known to enforce promoter-proximal pausing of RNA polymerase II (Pol II), a pervasive phenomenon observed across multicellular genomes. However, the physiological impact of NELF on tissue homeostasis remains unclear. Here, we show that whole-body conditional deletion of the B subunit of NELF (NELF-B) in adult mice results in cardiomyopathy and impaired response to cardiac stress. Tissue-specific knockout of NELF-B confirms its cell-autonomous function in cardiomyocytes. NELF directly supports transcription of those genes encoding rate-limiting enzymes in fatty acid oxidation (FAO) and the tricarboxylic acid (TCA) cycle. NELF also shares extensively transcriptional target genes with peroxisome proliferator-activated receptor α (PPARα), a master regulator of energy metabolism in the myocardium. Mechanistically, NELF helps stabilize the transcription initiation complex at the metabolism-related genes. Our findings strongly indicate that NELF is part of the PPARα-mediated transcription regulatory network that maintains metabolic homeostasis in cardiomyocytes. 2014-03-20 2014-04-10 /pmc/articles/PMC4277258/ /pubmed/24656816 http://dx.doi.org/10.1016/j.celrep.2014.02.028 Text en © 2014 The Authors http://creativecommons.org/licenses/by-nc-nd/3.0/ This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/3.0/). |
spellingShingle | Article Pan, Haihui Qin, Kunhua Guo, Zhanyong Ma, Yonggang April, Craig Gao, Xiaoli Andrews, Thomas G. Bokov, Alex Zhang, Jianhua Chen, Yidong Weintraub, Susan T. Fan, Jian-Bing Wang, Degeng Hu, Yanfen Aune, Gregory J. Lindsey, Merry L. Li, Rong Negative Elongation Factor Controls Energy Homeostasis in Cardiomyocytes |
title | Negative Elongation Factor Controls Energy Homeostasis in Cardiomyocytes |
title_full | Negative Elongation Factor Controls Energy Homeostasis in Cardiomyocytes |
title_fullStr | Negative Elongation Factor Controls Energy Homeostasis in Cardiomyocytes |
title_full_unstemmed | Negative Elongation Factor Controls Energy Homeostasis in Cardiomyocytes |
title_short | Negative Elongation Factor Controls Energy Homeostasis in Cardiomyocytes |
title_sort | negative elongation factor controls energy homeostasis in cardiomyocytes |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4277258/ https://www.ncbi.nlm.nih.gov/pubmed/24656816 http://dx.doi.org/10.1016/j.celrep.2014.02.028 |
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