Akashi Makoto, Okamoto Akihiko, Tsuchiya Yoshiki, Todo Takeshi, Nishida Eisuke, Node Koichi
The Research Institute for Time Studies, Yamaguchi University, Yamaguchi 753-8511, Japan.
The Research Institute for Time Studies, Yamaguchi University, Yamaguchi 753-8511, Japan.
Cell Rep. 2014 May 22;7(4):1056-64. doi: 10.1016/j.celrep.2014.03.072. Epub 2014 May 1.
In the current model of the mammalian circadian clock, PERIOD (PER) represses the activity of the circadian transcription factors BMAL1 and CLOCK, either independently or together with CRYPTOCHROME (CRY). Here, we provide evidence that PER has an entirely different function from that reported previously, namely, that PER inhibits CRY-mediated transcriptional repression through interference with CRY recruitment into the BMAL1-CLOCK complex. This indirect positive function of PER is consistent with previous data from genetic analyses using Per-deficient or mutant mice. Overall, our results support the hypothesis that PER plays different roles in different circadian phases: an early phase in which it suppresses CRY activity, and a later phase in which it acts as a transcriptional repressor with CRY. This buffering effect of PER on CRY might help to prolong the period of rhythmic gene expression. Additional studies are required to carefully examine the promoter- and phase-specific roles of PER.
在当前哺乳动物生物钟模型中，周期蛋白（PER）独立地或与隐花色素（CRY）一起抑制生物钟转录因子BMAL1和CLOCK的活性。在此，我们提供证据表明，PER具有与先前报道的完全不同的功能，即PER通过干扰CRY募集到BMAL1 - CLOCK复合物中，抑制CRY介导的转录抑制。PER的这种间接正向功能与先前使用Per缺陷或突变小鼠进行的遗传分析数据一致。总体而言，我们的结果支持以下假设：PER在不同的生物钟阶段发挥不同的作用，在早期阶段它抑制CRY活性，而在后期阶段它与CRY一起作为转录抑制因子。PER对CRY的这种缓冲作用可能有助于延长节律性基因表达的周期。需要进一步研究仔细检查PER在启动子和特定阶段的作用。
