Center for Epigenetics and Metabolism, School of Medicine, University of California, Irvine, Irvine, CA, USA.
Cell Cycle. 2012 Sep 1;11(17):3304-11. doi: 10.4161/cc.21669. Epub 2012 Aug 16.
The circadian system controls a large array of physiological and metabolic functions. The molecular organization of the circadian clock is complex, involving various elements organized in feedback regulatory loops. Here we demonstrate that the RelB subunit of NFκB acts as a repressor of circadian transcription. RelB physically interacts with the circadian activator BMAL1 in the presence of CLOCK to repress circadian gene expression at the promoter of the clock-controlled gene Dbp. The repression is independent of the circadian negative regulator CRY. Notably, RelB -/- fibroblasts have profound alterations of circadian genes expression. These findings reveal a previously unforeseen function for RelB as an important regulator of the mammalian circadian system in fibroblasts.
生物钟系统控制着大量的生理和代谢功能。生物钟的分子组织非常复杂，涉及各种元素组成的反馈调节环。在这里，我们证明 NFκB 的 RelB 亚基作为生物钟转录的抑制剂。RelB 在 CLOCK 的存在下与生物钟激活剂 BMAL1 相互作用，从而在时钟控制基因 Dbp 的启动子处抑制生物钟基因的表达。这种抑制作用与生物钟负调节剂 CRY 无关。值得注意的是，RelB-/-成纤维细胞的生物钟基因表达发生了深刻的改变。这些发现揭示了 RelB 作为成纤维细胞中哺乳动物生物钟系统的重要调节剂的一个以前未被预见的功能。
