Grant: Discovery Grants Program - Individual

The growth and development of an organism is characterized by regulated transcription of specific sets of genes. Any deviation from normal expression pattern may lead to developmental abnormalities or a diseased state. A variety of stimuli such as environmental factors, developmental signals, pathogens and nutrients modulate gene expression. The stimuli are often perceived by the cell surface and are transduced inside the cell where they activate or repress specific genes by targeting gene-specific transcription factors. The transcription regulators are recruited to the distal regulatory elements of their cognate genes in a DNA-sequence specific manner. They act in conjunction with the regulatory molecules called 'cofactors'. The activation domain of activators directly interacts with cofactors and facilitates their recruitment to the gene regulatory regions. The cofactors can exert gene activation in two principal ways: (1) by modifying chromatin structure thereby making DNA accessible to transcription complex and (2) by directly stimulating binding of RNAP II and general transcription factors to the promoter. An in-depth understanding of role of cofactors is obligatory for a thorough understanding of gene activation in eukaryotes. I have chosen to study regulation of URA3 gene of budding yeast in response to presence or absence of a nutrient component uracil in the medium. The proposed work will provide insights into the cooperative interaction of cofactors during signal-induced transcriptional activation of URA3 gene. The work will serve as a paradigm to understand gene regulation during development and diseased state in higher eukaryotes.