Westermark Pål O
Institute for Theoretical Biology, Charité -Universitätsmedizin Berlin, Berlin, Germany.
PLoS Genet. 2016 Aug 9;12(8):e1006231. doi: 10.1371/journal.pgen.1006231. eCollection 2016 Aug.
Circadian rhythms in transcription are generated by rhythmic abundances and DNA binding activities of transcription factors. Propagation of rhythms to transcriptional initiation involves the core promoter, its chromatin state, and the basal transcription machinery. Here, I characterize core promoters and chromatin states of genes transcribed in a circadian manner in mouse liver and in Drosophila. It is shown that the core promoter is a critical determinant of circadian mRNA expression in both species. A distinct core promoter class, strong circadian promoters (SCPs), is identified in mouse liver but not Drosophila. SCPs are defined by specific core promoter features, and are shown to drive circadian transcriptional activities with both high averages and high amplitudes. Data analysis and mathematical modeling further provided evidence for rhythmic regulation of both polymerase II recruitment and pause release at SCPs. The analysis provides a comprehensive and systematic view of core promoters and their link to circadian mRNA expression in mouse and Drosophila, and thus reveals a crucial role for the core promoter in regulated, dynamic transcription.
转录中的昼夜节律是由转录因子的节律性丰度和DNA结合活性产生的。节律向转录起始的传播涉及核心启动子、其染色质状态和基础转录机制。在这里,我对小鼠肝脏和果蝇中以昼夜节律方式转录的基因的核心启动子和染色质状态进行了表征。结果表明,核心启动子是这两个物种中昼夜节律性mRNA表达的关键决定因素。在小鼠肝脏中鉴定出了一种独特的核心启动子类别,即强昼夜节律启动子(SCP),但在果蝇中未发现。SCP由特定的核心启动子特征定义,并被证明能驱动具有高平均值和高振幅的昼夜节律转录活性。数据分析和数学建模进一步提供了证据,证明在SCP处聚合酶II募集和暂停释放均受到节律性调控。该分析提供了关于核心启动子及其与小鼠和果蝇中昼夜节律性mRNA表达之间联系的全面而系统的观点,从而揭示了核心启动子在受调控的动态转录中的关键作用。