GENE EXPRESSION DURING SPORULATION

描述(申请人提供)：细胞分化是一个基本的生物学过程。它的核心是在不同类型的细胞中建立不同的基因表达程序，以及基因表达与形态变化的协调。枯草芽孢杆菌芽胞形成是一种原始的细胞分化系统，由于其遗传操作简单，已成为原核生物细胞分化研究的范例。所有芽胞形成的关键调节因子也在所有已测序的芽孢菌科物种中确定，包括病原体炭疽芽孢杆菌和艰难梭菌。产孢子包括分裂成两种不同的细胞类型，母细胞和前孢子。前孢子被母细胞吞噬，发育成成熟的、抗性的孢子。孢子形成需要四种RNA聚合酶sigma因子的作用，在前孢子中依次为sigmaF和sigmaG，在母细胞中为sigmaE。这里的主要目标是了解基因表达是如何建立和维持的，以及基因表达是如何与形态变化相协调的。大多数提案都集中在枯草杆菌上。将开展一系列相互关联的研究工作。有人建议研究在spollA Delta突变体中，sigmaG活性从前孢子转移到母细胞的原因。建议使用我们开发的两部分区隔试验来鉴定和鉴定前孢子特异性表达所需的分裂基因和SF激活调节因子。有人建议调查为什么某些SF定向的基因在染色体末端附近重新定位时表达很差。有人建议对参与SigmaF和SigmaG活性时间控制的基因进行鉴定和鉴定。与芽孢杆菌和梭状芽孢杆菌的严重不对称位置相反，有人建议研究尿素芽孢杆菌中产孢子分裂位于中间位置的区划的建立。

DESCRIPTION (provided by applicant): Cell differentiation is a fundamental biological process. Central to it are the establishment of distinct programs of gene expression in the different cell types and the coordination of gene expression with morphological change. Formation of spores by Bacillus subtilis is a primitive system of cell differentiation that has become a paradigm for the study of cell differentiation in prokaryotes because of the ease of its genetic manipulation. All the key regulators of spore formation are also identified in all sequenced species of Bacillaceae, including the pathogens Bacillus anthracis and Clostridium difficile. Sporulation involves a characteristic division into two distinct cell types, the mother cell and the prespore. The prespore is engulfed by the mother cell and develops into the mature, resistant spore. Sporulation requires the action of four RNA polymerase sigma factors, sigmaF and then sigmaG in the prespore and sigmaE and then in sigmak the mother cell. The major objectives here are to understand how compartmentalized gene expression is established and maintained and how gene expression is coordinated with morphological change. Most of the proposal centers on B. subtilis. A series of interconnected lines of research will be pursued. It is proposed to investigate why sigmaG activity switches from the prespore to the mother cell in spollAdelta mutants. It is proposed to identify and characterize division genes and regulators of sF activation that are required for prespore-specific expression using a two-part compartmentalization test we have developed. It is proposed to investigate why certain sF-directed genes are poorly expressed when they are relocated near the chromosome terminus. It is proposed to identify and characterize genes involved in temporal control of sigmaF and sigmaG activity. It is proposed to investigate the establishment of compartmentalization in Sporosarcina ureae where the sporulation division is medially located, in contrast to its grossly asymmetric location for species of Bacillus and Clostridium.