Cargando…

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...

Descripción completa

Detalles Bibliográficos
Autores principales: 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
Formato: Online Artículo Texto
Lenguaje:English
Publicado: 2014
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
_version_ 1782350362269712384
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
work_keys_str_mv AT panhaihui negativeelongationfactorcontrolsenergyhomeostasisincardiomyocytes
AT qinkunhua negativeelongationfactorcontrolsenergyhomeostasisincardiomyocytes
AT guozhanyong negativeelongationfactorcontrolsenergyhomeostasisincardiomyocytes
AT mayonggang negativeelongationfactorcontrolsenergyhomeostasisincardiomyocytes
AT aprilcraig negativeelongationfactorcontrolsenergyhomeostasisincardiomyocytes
AT gaoxiaoli negativeelongationfactorcontrolsenergyhomeostasisincardiomyocytes
AT andrewsthomasg negativeelongationfactorcontrolsenergyhomeostasisincardiomyocytes
AT bokovalex negativeelongationfactorcontrolsenergyhomeostasisincardiomyocytes
AT zhangjianhua negativeelongationfactorcontrolsenergyhomeostasisincardiomyocytes
AT chenyidong negativeelongationfactorcontrolsenergyhomeostasisincardiomyocytes
AT weintraubsusant negativeelongationfactorcontrolsenergyhomeostasisincardiomyocytes
AT fanjianbing negativeelongationfactorcontrolsenergyhomeostasisincardiomyocytes
AT wangdegeng negativeelongationfactorcontrolsenergyhomeostasisincardiomyocytes
AT huyanfen negativeelongationfactorcontrolsenergyhomeostasisincardiomyocytes
AT aunegregoryj negativeelongationfactorcontrolsenergyhomeostasisincardiomyocytes
AT lindseymerryl negativeelongationfactorcontrolsenergyhomeostasisincardiomyocytes
AT lirong negativeelongationfactorcontrolsenergyhomeostasisincardiomyocytes