RNA Polymerase and Bacterial Differentiation

描述（由申请人提供）：当枯草芽孢杆菌从营养形态分化为休眠的内孢子时，会发生复杂的形态和生理变化，需要许多基因的表达。在此过程中，四种新的RNA聚合酶sigma亚基出现相互取代，并赋予RNA聚合酶识别不同类型启动子的不同特异性。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结合蛋白控制，从而影响时间和细胞类型特异性转录。产孢细菌被分成两个室（前孢子和母细胞），在这两个室中表达不同的基因。除了孢子特异性诱导sigma因子合成外，各sigma因子的活性也受到调控。在发育过程中，sigma因子活性的调节用于同步两个细胞区室中不同的基因表达程序。协调前孢子和母细胞中sigma因子活动的机制尚不完全清楚，但似乎涉及将蛋白质靶向到特定的亚细胞位置，在那里它们提供细胞间信号传导的管道。我们将研究Spo0A（一种DNA结合蛋白）激活启动子的机制，以了解它如何与两种不同的sigma因子相互作用以影响启动子的时间和细胞类型特异性激活。我们还将研究母细胞和前孢子中信号蛋白之间的细胞间信号传导机制，特别是将母细胞中产生的信号蛋白和其他蛋白靶向前孢子的机制。阐明枯草芽孢杆菌中控制基因时间表达的机制，以及基因表达的同步发育程序，可能会导致发现不仅在孢子形成病原体中，而且在各种微生物中调节基因表达的新机制。

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.