Abstract
Nuclear hormone receptor function is controlled by a number of ancillary factors termed coregulators. Such coactivators and corepressors afford considerable flexibility in the coordinate expression of gene networks in numerous physiological, developmental and metabolic processes. PGC-1α, originally described as transcriptional coactivator of PPARγ, has since been shown to act in a much broader context. PGC-1α coordinates the transcriptional programs of several key cellular pathways including mitochondrial biogenesis, thermogenesis, hepatic gluconeogenesis and β- oxidation of fatty acids via interactions with a growing number of transcription factors. A central issue to understand the diverse functions of PGC-1α is to gain insight into the mechanisms that confer specificity to its interactions with transfactors in response to intra- and extracellular signals. This review focuses on the different modes of regulation of PGC-1α function and the implications for tissue and context-specific transcriptional responses. Moreover, the role of sequence substitutions at the PGC-1α gene locus and their haplotype structure is discussed in relation to human disease phenotypes.
Keywords: coregulators, nuclear hormone receptors, mitochondrial biogenesis, energy metabolism
Current Genomics
Title: PGC-1α: A Multifunctional Transcriptional Coactivator Involved in Human Metabolic Disorders
Volume: 5 Issue: 5
Author(s): H. Oberkofler, F. Krempler and W. Patsch
Affiliation:
Keywords: coregulators, nuclear hormone receptors, mitochondrial biogenesis, energy metabolism
Abstract: Nuclear hormone receptor function is controlled by a number of ancillary factors termed coregulators. Such coactivators and corepressors afford considerable flexibility in the coordinate expression of gene networks in numerous physiological, developmental and metabolic processes. PGC-1α, originally described as transcriptional coactivator of PPARγ, has since been shown to act in a much broader context. PGC-1α coordinates the transcriptional programs of several key cellular pathways including mitochondrial biogenesis, thermogenesis, hepatic gluconeogenesis and β- oxidation of fatty acids via interactions with a growing number of transcription factors. A central issue to understand the diverse functions of PGC-1α is to gain insight into the mechanisms that confer specificity to its interactions with transfactors in response to intra- and extracellular signals. This review focuses on the different modes of regulation of PGC-1α function and the implications for tissue and context-specific transcriptional responses. Moreover, the role of sequence substitutions at the PGC-1α gene locus and their haplotype structure is discussed in relation to human disease phenotypes.
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Cite this article as:
Oberkofler H., Krempler F. and Patsch W., PGC-1α: A Multifunctional Transcriptional Coactivator Involved in Human Metabolic Disorders, Current Genomics 2004; 5 (5) . https://dx.doi.org/10.2174/1389202043349129
DOI https://dx.doi.org/10.2174/1389202043349129 |
Print ISSN 1389-2029 |
Publisher Name Bentham Science Publisher |
Online ISSN 1875-5488 |
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