Department of Microbiology, College of Biological Sciences, University of California, Davis, California 95616, USA.
J Biol Chem. 2011 Dec 30;286(52):44988-99. doi: 10.1074/jbc.M111.291625. Epub 2011 Nov 7.
The SMRT and NCoR corepressors partner with, and help mediate repression by, a wide variety of nuclear receptors and non-receptor transcription factors. Both SMRT and NCoR are expressed by alternative mRNA splicing, resulting in the production of a series of interrelated corepressor variants that differ in their tissue distribution and in their biochemical properties. We report here that different corepressor splice variants can exert opposing transcriptional and biological effects during adipocyte differentiation. Most notably, the NCoRω splice variant inhibits, whereas the NCoRδ splice variant promotes, adipogenesis. Furthermore, the ratio of NCoRω to NCoRδ decreases during adipogenic differentiation. We propose that this alteration in corepressor splicing helps convert the cellular transcriptional program from one that maintains the pre-adipocyte in an undifferentiated state to a new transcriptional context that promotes differentiation and helps establish the proper physiology of the mature adipocyte.
SMRT 和 NCoR 共抑制因子与多种核受体和非受体转录因子结合，并帮助它们介导抑制作用。SMRT 和 NCoR 均可通过选择性剪接表达，产生一系列相关的共抑制因子变体，这些变体在组织分布和生化特性上存在差异。我们在此报告，在脂肪细胞分化过程中，不同的共抑制因子剪接变体可发挥相反的转录和生物学效应。值得注意的是，NCoRω 剪接变体抑制脂肪生成，而 NCoRδ 剪接变体促进脂肪生成。此外，在脂肪生成分化过程中，NCoRω 与 NCoRδ 的比例降低。我们提出，这种共抑制因子剪接的改变有助于将细胞的转录程序从维持前脂肪细胞未分化状态转变为促进分化并有助于建立成熟脂肪细胞的正常生理状态的新转录环境。
