FoxO6 and PGC-1α form a regulatory loop in myogenic cells
| Autor: | Szu Tah Chen, Wei Chieh Huang, Hsiang Cheng Chi, Hui Peng Yu, Mu Shiun Tsai, Shih Ying Chung, Kai Min Huang, Shen Liang Chen, Ching Wen Su, Kuan Wei Lee, Cheng Tao Lin |
|---|---|
| Rok vydání: | 2013 |
| Předmět: |
Male
muscle PGC-1α FOXO1 FoxO forkhead box O Biochemistry DMEM Dulbecco’s modified Eagle’s medium PBST PBS containing 0.5% Tween 20 Myoblasts Mice Transcription (biology) oxidative metabolism GM growth medium Promoter Regions Genetic Receptor Regulation of gene expression HRP horseradish peroxidase FOXO Family Forkhead Transcription Factors GC gastrocnemius Peroxisome Proliferator-Activated Receptor Gamma Coactivator 1-alpha FoxO6 medicine.anatomical_structure HEK-293T HEK-293 cells expressing the large T-antigen of SV40 transcription Oxidation-Reduction PI3k phosphoinositide 3-kinase MBP maltose-binding protein Biophysics Oxidative phosphorylation Biology S2 DM differentiation medium EMSA electrophoretic mobility-shift assay Cell Line Physical Conditioning Animal CHIP chromatin immunoprecipitation medicine Animals Humans Molecular Biology Transcription factor Original Paper promoter Base Sequence PGC-1α peroxisome-proliferator-activated receptor γ co-activator 1α Skeletal muscle Cell Biology Gapdh glyceraldehydes-3-phosphate dehydrogenase Molecular biology T2D type 2 diabetes Gene Expression Regulation FCS fetal calf serum MRFs myogenic regulatory factors qRT-PCR quantitative reverse transcription PCR Transcription Factors |
| Zdroj: | Bioscience Reports |
| ISSN: | 1573-4935 0144-8463 |
| DOI: | 10.1042/bsr20130031 |
| Popis: | Transcription factors of the FoxO (forkhead box O) family regulate a wide range of cellular physiological processes, including metabolic adaptation and myogenic differentiation. The transcriptional activity of most FoxO members is inhibitory to myogenic differentiation and overexpression of FoxO1 inhibits the development of oxidative type I fibres in vivo. In this study, we found that FoxO6, the last discovered FoxO family member, is expressed ubiquitously in various tissues but with higher expression levels in oxidative tissues, such as brain and oxidative muscles. Both the expression level and promoter activity of FoxO6 were found to be enhanced by PGC-1α (peroxisome-proliferator-activated receptor γ co-activator 1α), thus explained its enriched expression in oxidative tissues. We further demonstrated that FoxO6 represses the expression of PGC-1α via direct binding to an upstream A/T-rich element (AAGATATCAAAACA,−2228–2215) in the PGC-1α promoter. Oxidative low-intensity exercise induced PGC-1α but reduced FoxO6 expression levels in hind leg muscles, and the binding of FoxO6 to PGC-1α promoter was also prevented by exercise. As FoxO6 promoter can be co-activated by PGC-1α and its promoter in turn can be repressed by FoxO6, it suggests that FoxO6 and PGC-1α form a regulatory loop for setting oxidative metabolism level in the skeletal muscle, which can be entrained by exercise. |
| Databáze: | OpenAIRE |
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