國家衛生研究院 NHRI:Item 3990099045/8749

NHRI > Institute of Molecular and Genomic Medicine > Gan-Guang Liou(2006-2014) > Periodical Articles > Item 3990099045/8749

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Title:	Bhlhe40 represses PGC-1alpha activity on metabolic gene promoters in myogenic cells
Other Titles:	Bhlhe40 represses PGC-1α activity on metabolic gene promoters in myogenic cells
Authors:	Chung, SY;Kao, CH;Villarroya, F;Chang, HY;Chang, HC;Hsiao, SP;Liou, GG;Chen, SL
Contributors:	Institute of Molecular and Genomic Medicine
Abstract:	PGC-1alpha is a transcriptional coactivator promoting oxidative metabolism in many tissues. Its expression in skeletal muscle (SKM) is induced by hypoxia and reactive oxidative species (ROS) generated during exercise, suggesting that PGC-1alpha might mediate the crosstalk between oxidative metabolism and cellular responses to hypoxia and ROS. Here we found that PGC-1alpha directly interacted with Bhlhe40, a bHLH transcriptional repressor induced by hypoxia and protects SKM from ROS damage, and they co-occupied PGC-1alpha targeted gene promoters/enhancers, which in turn repressed PGC-1alpha transactivational activity. Bhlhe40 repressed PGC-1alpha activity through recruiting HDACs and preventing the relief of PGC-1alpha intra-molecular repression caused by its own intrinsic suppressor domain. Knockdown of Bhlhe40 mRNA increased levels of ROS, fatty acid oxidation, mitochondria DNA, and the expression of PGC-1alpha target genes. Similar effects were also observed when the Bhlhe40 mediated repression was rescued by a dominantly active form of the PGC-1alpha-interacting domain (PID) from Bhlhe40. We further found that Bhlhe40 mediated repression can be largely relieved by exercise, in which its recruitment to PGC-1alpha targeted cis-elements were significantly reduced. These observations suggest that Bhlhe40 is a novel regulator of PGC-1alpha activity repressing oxidative metabolism gene expression and mitochondrion biogenesis in sedentary SKM.
Date:	2015-07
Relation:	Molecular and Cellular Biology. 2015 Jul;35(14):2518-2529.
Link to:	http://dx.doi.org/10.1128/mcb.00387-15
JIF/Ranking 2023:	http://gateway.webofknowledge.com/gateway/Gateway.cgi?GWVersion=2&SrcAuth=NHRI&SrcApp=NHRI_IR&KeyISSN=0270-7306&DestApp=IC2JCR
Cited Times(WOS):	https://www.webofscience.com/wos/woscc/full-record/WOS:000357457900012
Cited Times(Scopus):	http://www.scopus.com/inward/record.url?partnerID=HzOxMe3b&scp=84932603807
Appears in Collections:	[Gan-Guang Liou(2006-2014)] Periodical Articles

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