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FoxO6 and PGC-1α form a regulatory loop in myogenic cells
- Source :
- Bioscience Reports
- Publication Year :
- 2013
- Publisher :
- Portland Press Ltd., 2013.
-
Abstract
- 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.
- Subjects :
- 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
Subjects
Details
- ISSN :
- 15734935 and 01448463
- Volume :
- 33
- Database :
- OpenAIRE
- Journal :
- Bioscience Reports
- Accession number :
- edsair.doi.dedup.....4c5505e3864038a73cecff8278f79f95
- Full Text :
- https://doi.org/10.1042/bsr20130031