RNA Polymerase and Bacterial Differentiation

描述(申请人提供)：当枯草芽孢杆菌从繁殖体分化为休眠内孢子时，会发生复杂的形态和生理变化，需要许多基因的表达。在这个过程中，四个新的RNA聚合酶sigma亚基出现，相互取代，赋予RNA聚合酶不同的特异性，以识别不同类别的启动子。这些sigma因子按sigmaF、sigmaE、sigmaG和sigmaK的顺序出现。此外，RNA聚合酶对特定启动子的作用受DNA结合蛋白的控制，从而影响时间和细胞类型的特定转录。产孢子菌分为两个隔间(前孢子和母细胞)，在其中表达不同的基因。除了孢子形成特异性地诱导Sigma因子合成外，每个Sigma因子的活性都受到调节。在发育过程中，西格玛因子活性的调节被用来同步两个细胞间隔中不同的基因表达程序。在前孔和母细胞中协调Sigma因子活性的机制还不完全清楚，但似乎涉及到将蛋白质靶向到特定的亚细胞位置，在那里它们为细胞间信号传递提供管道。我们将研究DNA结合蛋白Spo0A激活启动子的机制，以了解它是如何与两个不同的sigma因子相互作用影响启动子的时间和细胞类型特异性激活的。我们还将研究母细胞中的SigmaE和前孔中的SigmaG之间的细胞间信号转导机制，特别是针对母细胞中的信号蛋白和其他信号蛋白到前孔的机制。阐明枯草芽孢杆菌中控制基因时间表达和同步基因表达发育程序的机制可能会导致发现新的机制，不仅在内孢子形成病原体中调控基因表达，而且在多种微生物中也调控基因表达。

DESCRIPTION (provided by applicant): As the bacterium Bacillus subtilis differentiates from the vegetative form into a dormant endospore, complex morphological and physiological changes occur that require the expression of many genes. During the process, four new RNA polymerase sigma subunits appear displacing one another and conferring on the RNA polymerase different specificities for the recognition of different classes of promoters. These sigma factors appear in the order sigmaF, sigmaE, sigmaG, and sigmaK. In addition, the action of RNA polymerase on specific promoters is controlled by DNA binding proteins to affect both temporal and cell-type specific transcription. The sporulating bacterium is divided into two compartments (forespore and mothercell) within which different sets of genes are expressed. In addition to the sporulation-specific induction of sigma factor synthesis, the activity of each sigma factor is regulated. Regulation of sigma factor activity is used to synchronize the different programs of gene expression in the two cellular compartments during development. The mechanisms that coordinate sigma factor activities in the forespore and mothercell are not completely understood, but appear to involve targeting of proteins to specific subcellular locations where they provide the conduits for intercellular signaling. We will investigate the mechanisms of promoter activation by Spo0A, a DNA binding protein, to understand how it interacts with two different sigma factors to affect both temporal and cell-type specific activation of promoters. We will also investigate the mechanisms involved in the intercellular signaling between sigmaE in the mothercell and sigmaG in the forespore, especially the mechanisms that target the signaling proteins and others made in the mothercell to the forespore. Elucidation of the mechanisms that control the temporal expression of genes, and synchronize developmental programs of gene expression in Bacillus subtilis may lead to the discovery of novel mechanisms that regulate gene expression not only in endospore-forming pathogens but also in a wide variety of microorganisms.