Howard Hughes Medical Institute, Harvard University Faculty of Arts and Sciences Center for Systems Biology, Cambridge, MA 02138, USA; Department of Molecular and Cellular Biology, Harvard University, Cambridge, MA 02138, USA.
Howard Hughes Medical Institute, Harvard University Faculty of Arts and Sciences Center for Systems Biology, Cambridge, MA 02138, USA; Department of Molecular and Cellular Biology, Harvard University, Cambridge, MA 02138, USA; Department of Chemistry and Chemical Biology, Harvard University, Cambridge, MA 02138, USA.
Cell Rep. 2018 Dec 11;25(11):2937-2945.e3. doi: 10.1016/j.celrep.2018.11.049.
The circadian clock of the cyanobacterium Synechococcus elongatus PCC 7942 drives oscillations in global mRNA abundances with 24-hr periodicity under constant light conditions. The circadian clock-regulated transcription factor RpaA controls the timing of circadian gene expression, but the mechanisms underlying this control are not well understood. Here, we show that four RpaA-dependent sigma factors-RpoD2, RpoD6, RpoD5, and SigF2-are sequentially activated downstream of active RpaA and are required for proper expression of circadian mRNAs. By measuring global gene expression in strains modified to individually lack rpoD2, rpoD6, rpoD5, and sigF2, we identify how expression of circadian mRNAs, including sigma factor mRNAs, is altered in the absence of each sigma factor. Broadly, our findings suggest that a single transcription factor, RpaA, is sufficient to generate complex circadian expression patterns in part by regulating an interdependent sigma factor cascade.
在持续光照条件下,蓝藻集胞藻 PCC 7942 的生物钟驱动全球 mRNA 丰度以 24 小时为周期的振荡。生物钟调节转录因子 RpaA 控制生物钟基因表达的时间,但这种控制的机制尚不清楚。在这里,我们表明,四个 RpaA 依赖性σ因子(RpoD2、RpoD6、RpoD5 和 SigF2)在活性 RpaA 下游依次被激活,并且对于正确表达生物钟 mRNA 是必需的。通过测量分别修饰 rpoD2、rpoD6、rpoD5 和 sigF2 的菌株中的全局基因表达,我们确定了在缺失每个σ因子的情况下,生物钟 mRNA(包括σ因子 mRNA)的表达如何改变。总的来说,我们的研究结果表明,单个转录因子 RpaA 通过调节相互依赖的σ因子级联反应足以产生复杂的生物钟表达模式。