12-h clock regulation of genetic information flow by XBP1s
12-h clock regulation of genetic information flow by XBP1s
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DOI：
10.1371/journal.pbio.3000580
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发表时间：
2020-01-01
期刊：
影响因子：
9.8
通讯作者：
Zhu, Bokai
中科院分区：
文献类型：
--
作者：
Pan, Yinghong;Ballance, Heather;Zhu, Bokai
我们的小组最近的特点是细胞自主哺乳动物12小时时钟独立于昼夜节律钟，但其功能和调节机制仍然知之甚少。在这里，我们表明，在小鼠肝脏中，转录调控显着有助于建立12小时的mRNA表达的节奏依赖于剪接形式的X-box结合蛋白1（XBP 1 s）的方式。从机制上讲，XBP 1 s启动子结合位点的基序严格性决定了XBP 1 s在黎明和黄昏驱动新生mRNA转录的12小时节律的能力，这对于基础转录调节、mRNA加工和输出、核糖体生物合成、翻译起始、和内质网（ER）中的蛋白质加工/分选-高尔基体的时间顺序与中心法则信息流（CEDIF）所描述的渐进式分子加工序列一致。我们进一步确定了GA结合蛋白（GABPs）作为推定的新的转录调节驱动12小时的基因表达的节奏与更多样化的阶段。这些12小时的基因表达节律是细胞自主的，在海洋动物中具有昼夜节律钟的进化保守。我们的研究结果表明，哺乳动物12小时时钟介导的不同的生物学途径的转录控制进化保守，错综复杂的网络。我们推测，12小时的时钟是增选，以适应哺乳动物在两个高峰时间的基因表达和处理的提高，与特定的基因处理在每个高峰时间调节的昼夜节律和/或组织特异性途径。
Our group recently characterized a cell-autonomous mammalian 12-h clock independent from the circadian clock, but its function and mechanism of regulation remain poorly understood. Here, we show that in mouse liver, transcriptional regulation significantly contributes to the establishment of 12-h rhythms of mRNA expression in a manner dependent on Spliced Form of X-box Binding Protein 1 (XBP1s). Mechanistically, the motif stringency of XBP1s promoter binding sites dictates XBP1s's ability to drive 12-h rhythms of nascent mRNA transcription at dawn and dusk, which are enriched for basal transcription regulation, mRNA processing and export, ribosome biogenesis, translation initiation, and protein processing/sorting in the Endoplasmic Reticulum (ER)-Golgi in a temporal order consistent with the progressive molecular processing sequence described by the central dogma information flow (CEDIF). We further identified GA-binding proteins (GABPs) as putative novel transcriptional regulators driving 12-h rhythms of gene expression with more diverse phases. These 12-h rhythms of gene expression are cell autonomous and evolutionarily conserved in marine animals possessing a circatidal clock. Our results demonstrate an evolutionarily conserved, intricate network of transcriptional control of the mammalian 12-h clock that mediates diverse biological pathways. We speculate that the 12-h clock is coopted to accommodate elevated gene expression and processing in mammals at the two rush hours, with the particular genes processed at each rush hour regulated by the circadian and/or tissue-specific pathways.