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FoxO6 and PGC-1α form a regulatory loop in myogenic cells

Authors :
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
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.

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