期刊名称：Proceedings of the National Academy of Sciences
印刷版ISSN：0027-8424
电子版ISSN：1091-6490
出版年度：2004
卷号：101
期号：17
页码：6570-6575
DOI：10.1073/pnas.0401401101
语种：English
出版社：The National Academy of Sciences of the United States of America
摘要：Recent studies have shown that genes involved in oxidative phosphorylation (OXPHOS) exhibit reduced expression in skeletal muscle of diabetic and prediabetic humans. Moreover, these changes may be mediated by the transcriptional coactivator peroxisome proliferator-activated receptor {gamma} coactivator-1{alpha} (PGC-1{alpha}). By combining PGC-1{alpha}-induced genome-wide transcriptional profiles with a computational strategy to detect cis-regulatory motifs, we identified estrogen-related receptor {alpha} (Err{alpha}) and GA repeat-binding protein {alpha} as key transcription factors regulating the OXPHOS pathway. Interestingly, the genes encoding these two transcription factors are themselves PGC-1{alpha}-inducible and contain variants of both motifs near their promoters. Cellular assays confirmed that Err{alpha} and GA-binding protein a partner with PGC-1{alpha} in muscle to form a double-positive-feedback loop that drives the expression of many OXPHOS genes. By using a synthetic inhibitor of Err{alpha
