Prokaryotic gene regulation by light and oxygen

描述（由申请人提供）：氧张力的改变影响所有细胞类型的基因表达。在细菌系统中，氧气调节各种参与有氧和无氧能量代谢的基因。代谢过程，如碳固定、氮固定、呼吸和光合作用是根据氧气的存在或缺乏而调节的。在酵母和藻类细胞中，氧气会影响氧化防御基因和代谢酶的转录。在哺乳动物细胞中，越来越多的基因被认为是受氧调节的，比如血管生长因子，它是由原有血管合成新的毛细血管芽的关键调节因子。除了生理作用外，这些生长因子还参与疾病过程，如肿瘤生长过程中毛细血管形成的刺激。这一建议的重点是阐明细菌荚膜红杆菌和球形红杆菌如何能够感知氧张力的变化，并在响应中改变基因表达的分子细节。这些相关物种能够在各种能量产生模式下生长，包括有氧呼吸，厌氧发酵和光合作用。参与这些过程的基因的表达受到氧张力变化以及光强度变化的影响。众所周知，光对细胞生理的调节也发生在从细菌到哺乳动物的许多生物体中，这是本提案研究的第二个过程。事实上，在这个提议中研究的一个关键的氧调节转录因子也受到光强度的调节。作为研究氧和光调控基因表达的模式系统，我们重点研究了四吡咯的生物合成过程。这一途径受到氧气和光强度的高度调节，并负责产生B12、血红素和叶绿素等重要代谢物。

DESCRIPTION (provided by applicant): Alteration in oxygen tension affects gene expression in all cell types. In bacterial systems, oxygen regulates a variety of genes involved in aerobic versus anaerobic energy metabolism. Metabolic processes such as carbon fixation, nitrogen fixation, respiration and photosynthesis are regulated in response to the presence or absence of oxygen. In yeast and algal cells, oxygen is known to affect transcription of oxidative defense genes as well as metabolic enzymes. In mammalian cells, a growing number of genes are known to be oxygen regulated such as vascular growth factors that are key regulators for the synthesis of new capillary sprouts from preexisting vessels. Besides physiological roles, these growth factors are involved in disease processes such as the stimulation of capillary formation during tumor growth. This proposal is centered on elucidating molecular details of how bacteria Rhodobacter capsulatus and Rhodobacter sphaeroides are able to sense changes in oxygen tension, and in response, alter gene expression. These related species are capable of growth in a variety of energy generating modes including aerobic respiration, anaerobic fermentation and photosynthesis. The expression of genes involved in each of these processes are affected by alterations in oxygen tension, as well as by variations in light intensity. Regulation of cell physiology by light is also known to occur in a number of organisms ranging from bacterial to mammals and is a second process that is studied by this proposal. Indeed, one of the key oxygen regulated transcription factors studied in this proposal is also regulated by light intensity. As a model system for studying both oxygen and light regulation of gene expression, we have focused on the process of tetrapyrrole biosynthesis. This pathway is highly regulated by oxygen and light intensity and is responsible for the production of such important metabolites as B12, heme and chlorophylls.