NDLI: Errα and Gabpa/b specify PGC-1α-dependent oxidative phosphorylation gene expression that is altered in diabetic muscle

Content Provider	PubMed Central
Author	Mootha, Vamsi K. Handschin, Christoph Arlow, Dan Xie, Xiaohui Pierre, Julie St Smita, Sihag Yang, Wenli Altshuler, David Puigserver, Pere Patterson, Nick Willy, Patricia J. Schulman, Ira G. Heyman, Richard A. Lander, Eric S. Spiegelman, Bruce M.
Copyright Year	2004
Abstract	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 γ coactivator-1α (PGC-1α). By combining PGC-1α-induced genome-wide transcriptional profiles with a computational strategy to detect cis-regulatory motifs, we identified estrogen-related receptor α (Errα) and GA repeat-binding protein α as key transcription factors regulating the OXPHOS pathway. Interestingly, the genes encoding these two transcription factors are themselves PGC-1α-inducible and contain variants of both motifs near their promoters. Cellular assays confirmed that Errα and GA-binding protein a partner with PGC-1α in muscle to form a double-positive-feedback loop that drives the expression of many OXPHOS genes. By using a synthetic inhibitor of Errα, we demonstrated its key role in PGC-1α-mediated effects on gene regulation and cellular respiration. These results illustrate the dissection of gene regulatory networks in a complex mammalian system, elucidate the mechanism of PGC-1α action in the OXPHOS pathway, and suggest that Errα agonists may ameliorate insulin-resistance in individuals with type 2 diabetes mellitus.
Related Links	http://dx.doi.org/10.1073/pnas.0401401101
Ending Page	6575
Page Count	6
Starting Page	6570
File Format	PDF
ISSN	00278424
e-ISSN	10916490
Journal	Proceedings of the National Academy of Sciences of the United States of America
Issue Number	17
Volume Number	101
Language	English
Publisher	National Academy of Sciences
Publisher Date	2004-04-27
Access Restriction	Open
Rights Holder	National Academy of Sciences
Subject Keyword	General Research in Higher Education
Content Type	Text
Resource Type	Article
Subject	Multidisciplinary

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1	Ministry of Education (GoI), Department of Higher Education	Sanctioning Authority	https://www.education.gov.in/ict-initiatives
2	Indian Institute of Technology Kharagpur	Host Institute of the Project: The host institute of the project is responsible for providing infrastructure support and hosting the project	https://www.iitkgp.ac.in
3	National Digital Library of India Office, Indian Institute of Technology Kharagpur	The administrative and infrastructural headquarters of the project	Dr. B. Sutradhar bsutra@ndl.gov.in
4	Project PI / Joint PI	Principal Investigator and Joint Principal Investigators of the project	Dr. B. Sutradhar bsutra@ndl.gov.in Prof. Saswat Chakrabarti will be added soon
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