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. ? ? ?
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