Lin Jiandie D
Life Sciences Institute, Department of Cell and Developmental Biology, University of Michigan Medical Center, 210 Washtenaw Avenue, Ann Arbor, Michigan 48109, USA.
Mol Endocrinol. 2009 Jan;23(1):2-10. doi: 10.1210/me.2008-0344. Epub 2008 Nov 13.
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-gamma 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-gamma coactivator 1 networks in the regulation of chromatin-remodeling and mitochondrial oxidative metabolism.
转录共激活因子和共抑制因子正逐渐成为能量代谢及其他生物学过程的重要调节因子。这些因子通过与选择性转录因子相互作用以及募集染色质重塑复合物,对靶基因的转录发挥作用。近期对过氧化物酶体增殖物激活受体γ共激活因子1网络的遗传学和生物化学分析,为其在线粒体氧化代谢调控中的作用提供了新的机制见解。这些共激活因子响应营养信号和昼夜节律线索,整合组织代谢功能。与共激活因子相反,转录共抑制因子已被证明在线粒体生物发生和呼吸的控制中发挥相反作用。预计这些共激活因子和共抑制因子蛋白的平衡,更重要的是它们与特定转录伙伴的结合,将决定靶基因的表观遗传状态以及细胞的代谢表型。本综述重点介绍了过氧化物酶体增殖物激活受体γ共激活因子1网络在染色质重塑和线粒体氧化代谢调控中的生物学作用及机制基础。