Laboratory for Integrative and Systems Physiology, Ecole Polytechnique Fédérale de Lausanne, Lausanne CH-1015, Switzerland.
Genes Dev. 2013 Apr 15;27(8):819-35. doi: 10.1101/gad.214023.113.
Epigenetic regulation of gene expression is strongly influenced by the accessibility of nucleosomal DNA or the state of chromatin compaction. In this context, coregulators, including both coactivators and corepressors, are pivotal intermediates that bridge chromatin-modifying enzymes and transcription factors. NCoR1 (nuclear receptor corepressor) and SMRT (silencing mediator of retinoic acid and thyroid hormone receptor) are among the best-characterized corepressors from a molecular point of view. These coregulators have conserved orthologs in lower organisms, which underscores their functional importance. Here we summarize the results from recent in vivo studies that reveal the wide-ranging roles of NCoR1 and SMRT in developmental as well as homeostatic processes, including metabolism, inflammation, and circadian rhythms. We also discuss the potential implications of NCoR1 and SMRT regulation of pathways ranging from genomic stability and carcinogenesis to metabolic diseases such as type 2 diabetes.
基因表达的表观遗传调控受核小体 DNA 的可及性或染色质紧缩状态的强烈影响。在这种情况下，包括共激活因子和共抑制因子在内的共调节因子是连接染色质修饰酶和转录因子的关键中间产物。从分子角度来看，NCoR1（核受体共抑制因子）和 SMRT（维甲酸和甲状腺激素受体沉默介质）是研究最为深入的共抑制因子之一。这些共调节因子在低等生物中具有保守的同源物，这突出了它们的功能重要性。在这里，我们总结了最近的体内研究结果，这些结果揭示了 NCoR1 和 SMRT 在发育和稳态过程中的广泛作用，包括代谢、炎症和昼夜节律。我们还讨论了 NCoR1 和 SMRT 对从基因组稳定性和肿瘤发生到 2 型糖尿病等代谢疾病等多种途径的调节的潜在影响。
