ArticleMolecular and cellular biology2015
Bhlhe40 Represses PGC-1α Activity on Metabolic Gene Promoters in Myogenic Cells.
Article in Molecular and cellular biology, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 13 papers, 1 of them a synthesis that pooled it.
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Who cites it
13 citing papers in PubMed, 1 synthesis or guideline pooled it, 22 citations in OpenAlex.
- Time trajectories in the transcriptomic response to exercise - a meta-analysis.Nature communications · 2021Pooled it
- MyoD Over-Expression Rescues GST-bFGF Repressed Myogenesis.International journal of molecular sciences · 2024Article
- Hypoxia causes pancreatic β-cell dysfunction and impairs insulin secretion by activating the transcriptional repressor BHLHE40.EMBO reports · 2023Article
- Reciprocal Regulation of Peroxisome Biogenesis and Myogenic Factors Is Critical for Myogenesis.International journal of molecular sciences · 2023Article
- Semi-automated approach for generation of biological networks on drug-induced cholestasis, steatosis, hepatitis, and cirrhosis.Toxicological research · 2022Article
- 17β-Estradiol Inhibits Proliferation and Oxidative Stress in Vascular Smooth Muscle Cells by Upregulating BHLHE40 Expression.Frontiers in cardiovascular medicine · 2021Article
- Article
- MEHP interferes with mitochondrial functions and homeostasis in skeletal muscle cells.Bioscience reports · 2020Article
- Bhlhe40 differentially regulates the function and number of peroxisomes and mitochondria in myogenic cells.Redox biology · 2019Article
- BHLHE40 confers a pro-survival and pro-metastatic phenotype to breast cancer cells by modulating HBEGF secretion.Breast cancer research : BCR · 2018Article
- A map of the PGC-1α- and NT-PGC-1α-regulated transcriptional network in brown adipose tissue.Scientific reports · 2018Article
- Association of 5-hydroxymethylation and 5-methylation of DNA cytosine with tissue-specific gene expression.Epigenetics · 2017Article
- Responses of retinal and brain microvasculature to streptozotocin induced diabetes revealed by global expression profiling.Diabetes & vascular disease researchArticle
Corrections and comments
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Authors and funding
8 authors at 3 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
PGC-1α 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-1α might mediate the cross talk between oxidative metabolism and cellular responses to hypoxia and ROS. Here we found that PGC-1α directly interacted with Bhlhe40, a basic helix-loop-helix (bHLH) transcriptional repressor induced by hypoxia, and protects SKM from ROS damage, and they cooccupied PGC-1α-targeted gene promoters/enhancers, which in turn repressed PGC-1α transactivational activity. Bhlhe40 repressed PGC-1α activity through recruiting histone deacetylases (HDACs) and preventing the relief of PGC-1α intramolecular repression caused by its own intrinsic suppressor domain. Knockdown of Bhlhe40 mRNA increased levels of ROS, fatty acid oxidation, mitochondrial DNA, and expression of PGC-1α target genes. Similar effects were also observed when the Bhlhe40-mediated repression was rescued by a dominantly active form of the PGC-1α-interacting domain (PID) from Bhlhe40. We further found that Bhlhe40-mediated repression can be largely relieved by exercise, in which its recruitment to PGC-1α-targeted cis elements was significantly reduced. These observations suggest that Bhlhe40 is a novel regulator of PGC-1α activity repressing oxidative metabolism gene expression and mitochondrion biogenesis in sedentary SKM.
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