PDF(Pubmed)
Abstract：
Epigenetic regulation is important for circadian rhythm. In previous studies, multiple histone modifications were found at the Period (Per) locus. However, most of these studies were not conducted in clock neurons. In our screen, we found that a CoREST mutation resulted in defects in circadian rhythm by affecting Per transcription. Based on previous studies, we hypothesized that CoREST regulates circadian rhythm by regulating multiple histone modifiers at the Per locus. Genetic and physical interaction experiments supported these regulatory relationships. Moreover, through tissue-specific chromatin immunoprecipitation assays in clock neurons, we found that the CoREST mutation led to time-dependent changes in corresponding histone modifications at the Per locus. Finally, we proposed a model indicating the role of the CoREST complex in the regulation of circadian rhythm. This study revealed the dynamic changes of histone modifications at the Per locus specifically in clock neurons. Importantly, it provides insights into the role of epigenetic factors in the regulation of dynamic gene expression changes in circadian rhythm.
摘要：
表观遗传调节对昼夜节律很重要。在以往的研究中,在周期（每个）基因座发现了多个组蛋白修饰。然而,这些研究大多不是在时钟神经元中进行的。在我们的屏幕上,我们发现CoREST突变通过影响Per转录导致昼夜节律缺陷。根据以前的研究，我们假设CoREST通过调节Per位点的多个组蛋白修饰来调节昼夜节律。遗传和物理相互作用实验支持这些调节关系。此外，通过时钟神经元的组织特异性染色质免疫沉淀试验，我们发现CoREST突变导致Per基因座相应组蛋白修饰的时间依赖性变化。最后,我们提出了一个模型,表明CoREST复合体在昼夜节律调节中的作用.这项研究揭示了特定于时钟神经元的Per基因座组蛋白修饰的动态变化。重要的是,它提供了对表观遗传因素在昼夜节律动态基因表达变化调节中的作用的见解。
