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Life Sciences Institute and Department of Cell and Developmental Biology, University of Michigan Medical Center, Ann Arbor, Michigan 48109
Address all correspondence and requests for reprints to: Jiandie D. Lin, Ph.D., 5437 Life Sciences Institute, University of Michigan, 210 Washtenaw Avenue, Ann Arbor, Michigan 48109. E-mail: jdlin{at}umich.edu.
Transcriptional coactivators and corepressors are emerging as important regulators of energy metabolism and other biological processes. These factors exert their effects on the transcription of target genes through interaction with selective transcription factors and the recruitment of chromatin-remodeling complexes. Recent genetic and biochemical analyses of the peroxisomal proliferator-activated receptor-
coactivator 1 networks provide novel mechanistic insights regarding their role in the control of mitochondrial oxidative metabolism. These coactivators integrate tissue metabolic functions in response to nutritional signals as well as circadian timing cues. In contrast to coactivators, transcriptional corepressors have been demonstrated to play an opposite role in the control of mitochondrial biogenesis and respiration. The balance of these coactivator and corepressor proteins and, more importantly, their access to specific transcriptional partners are predicted to dictate the epigenetic states of target genes as well as the metabolic phenotype of the cells. This review highlights the biological role and mechanistic basis of the peroxisomal proliferator-activated receptor-
coactivator 1 networks in the regulation of chromatin-remodeling and mitochondrial oxidative metabolism.
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