Sancar Cigdem, Sancar Gencer, Ha Nati, Cesbron François, Brunner Michael
Heidelberg University Biochemistry Center, Heidelberg, Germany.
University of Heidelberg Biochemistry Center, Im Neuenheimer Feld 328, Heidelberg, D-69120, Germany.
BMC Biol. 2015 Feb 24;13:17. doi: 10.1186/s12915-015-0126-4.
Circadian clocks control rhythmic expression of a large number of genes in coordination with the 24 hour day-night cycle. The mechanisms generating circadian rhythms, their amplitude and circadian phase are dependent on a transcriptional network of immense complexity. Moreover, the contribution of post-transcriptional mechanisms in generating rhythms in RNA abundance is not known.
Here, we analyzed the clock-controlled transcriptome of Neurospora crassa together with temporal profiles of elongating RNA polymerase II. Our data indicate that transcription contributes to the rhythmic expression of the vast majority of clock-controlled genes (ccgs) in Neurospora. The ccgs accumulate in two main clusters with peak transcription and expression levels either at dawn or dusk. Dawn-phased genes are predominantly involved in catabolic and dusk-phased genes in anabolic processes, indicating a clock-controlled temporal separation of the physiology of Neurospora. Genes whose expression is strongly dependent on the core circadian activator WCC fall mainly into the dawn-phased cluster while rhythmic genes regulated by the glucose-dependent repressor CSP1 fall predominantly into the dusk-phased cluster. Surprisingly, the number of rhythmic transcripts increases about twofold in the absence of CSP1, indicating that rhythmic expression of many genes is attenuated by the activity of CSP1.
The data indicate that the vast majority of transcript rhythms in Neurospora are generated by dawn and dusk specific transcription. Our observations suggest a substantial plasticity of the circadian transcriptome with respect to the number of rhythmic genes as well as amplitude and phase of the expression rhythms and emphasize a major role of the circadian clock in the temporal organization of metabolism and physiology.
生物钟与24小时的昼夜循环相协调，控制着大量基因的节律性表达。产生昼夜节律的机制、其振幅和昼夜相位取决于一个极其复杂的转录网络。此外，转录后机制在RNA丰度产生节律中的作用尚不清楚。
在这里，我们分析了粗糙脉孢菌的生物钟控制转录组以及延伸的RNA聚合酶II的时间谱。我们的数据表明，转录有助于粗糙脉孢菌中绝大多数生物钟控制基因（ccgs）的节律性表达。ccgs聚集在两个主要簇中，转录和表达水平在黎明或黄昏达到峰值。黎明期基因主要参与分解代谢过程，而黄昏期基因主要参与合成代谢过程，这表明粗糙脉孢菌的生理机能存在生物钟控制的时间分离。其表达强烈依赖于核心生物钟激活因子WCC的基因主要落入黎明期簇，而受葡萄糖依赖性阻遏物CSP1调控的节律性基因主要落入黄昏期簇。令人惊讶的是，在没有CSP1的情况下，节律性转录本的数量增加了约两倍，这表明许多基因的节律性表达被CSP1的活性所减弱。
数据表明，粗糙脉孢菌中的绝大多数转录本节律是由黎明和黄昏特异性转录产生的。我们的观察结果表明，昼夜转录组在节律性基因的数量以及表达节律的振幅和相位方面具有显著的可塑性，并强调了生物钟在代谢和生理时间组织中的主要作用。
