Mammalian Period represses and de-represses transcription by displacing CLOCK-BMAL1 from promoters in a Cryptochrome-dependent manner
Mammalian Period represses and de-represses transcription by displacing CLOCK-BMAL1 from promoters in a Cryptochrome-dependent manner
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DOI：
10.1073/pnas.1612917113
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发表时间：
2016-10-11
影响因子：
11.1
通讯作者：
Sancar, Aziz
中科院分区：
文献类型：
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作者：
Chiou, Yi-Ying;Yang, Yanyan;Sancar, Aziz
哺乳动物的生物钟是以转录-翻译反馈环(TTFL)为基础的，该环由二级环巩固。在初级TTFL中，昼夜节律运动输出周期Kaput(Clock)-脑和肌肉Arnt-like Protein-1(BMAL1)异二聚体作为转录激活因子，而隐色素(Cry)和Period(PER)蛋白质作为抑制因子。PER通过以哭喊依赖的方式取代启动子中的CLOCK-BMAL1来抑制。有趣的是，具有复杂启动子的基因可以被PER抑制或解除抑制，这取决于特定的启动子调控元件。在这里，我们使用定义了时钟基因敲除突变的小鼠细胞系，RNA-SEQ，CHIP-SEQ和报告基因分析，以及核提取液中DNA-蛋白质相互作用的测量，以一种上下文相关的方式阐明了PER作为抑制物和去抑制物的双重功能。
The mammalian circadian clock is based on a transcription-translation feedback loop (TTFL) consolidated by secondary loops. In the primary TTFL, the circadian locomotor output cycles kaput (CLOCK)-brain and muscle Arnt-like protein-1 (BMAL1) heterodimer acts as the transcriptional activator, and Cryptochrome (CRY) and Period (PER) proteins function as repressors. PER represses by displacing CLOCK-BMAL1 from promoters in a CRY-dependent manner. Interestingly, genes with complex promoters may either be repressed or de-repressed by PER, depending on the particular promoter regulatory elements. Here, using mouse cell lines with defined knockout mutations in clock genes, RNA-seq, ChIP-seq, and reporter gene assays coupled with measurements of DNA-protein interactions in nuclear extracts, we elucidate the dual functions of PER as repressor and de-repressor in a context-dependent manner.