Regulation of Stress Induced Gene Expression in Saccharomyces Cerevisiae PDF Download

Author: Vasudha Bharatula
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Languages : en
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Book Description
Transcription initiation is complex process involving transcription factors(TF), co-activators, nucleosome remodelers and the pre-initiation complex (PIC);general transcription factors (GTF) and RNA polymerase II (RNAP2). The spatiotemporalorganization of these different proteins and their role in regulatingplasticity and selectivity of transcriptional reprogramming in various stressesremains unknown. I describe the role of Multicopy Suppressor of Snf1 mutation(Msn2); a stress responsive transcription factor, Mediator (coactivator) andnucleosome remodeling in fine-tuning gene expression in response to stress inyeast.Msn2 exhibits distinct patterns of nucleo-cytoplasmic oscillations indifferent stresses. I determined that Msn2 target genes exhibited fast or slowinduction kinetics in response to transient and persistent Msn2 nuclearoccupancy respectively. Chromatin immunoprecipitation studies revealed thatMsn2 binds promoters of common stress genes as well as condition specificgenes in nutrient and oxidative stresses, suggesting that TF dynamics could playa role in selective gene regulation in different stresses. Additionally, Msn2binding to ~30 oxidative genes was dependent on Yap1. However, deleting Msn2did not lead to a significant decrease in expression of oxidative stress responsegenes as did the absence of Yap1. These results suggest that indirectcooperativity between Msn2 and Yap1 could lead to selective promoter bindingbut the effects of such interactions on gene expression remain unclear.I studied the role of Mediator in native conditions, where its function has not been adequately addressed. Mediator occupies chromosomal interacting domains (CID), which mark boundaries between interacting genomic regions, suggesting that Mediator could play a significant role in higher-order genome organization along with functioning as a coactivator.Finally, I assessed the combined effect of Msn2, Mediator and nucleosome remodeling on gene expression upon nutrient deprivation. Both Msn2 and Mediator are selectively recruited to promoters of genes activated and repressed in nutrient stress. Genes activated by Msn2 exhibited rapid loss of nucleosomes, in an Msn2 dependent manner. In contrast, repression of genes was not accompanied by a significant gain in nucleosomes, suggesting additional mechanisms of repression could exist. The absence of Msn2, significantly decreased Mediator recruitment at promoters of target genes, indicating that Mediator- TF interactions are crucial for gene expression changes in stress. Interestingly, both RNAP2 and Mediator remained poised at promoters of repressed genes, possibly to re-initiate transcription once the stress has passed.These findings offer novel insights on how Msn2 regulates expression of specific genes depending on the environment by modulating its dynamics and genomic binding. The binding of Msn2 helps recruit Mediator and facilitate nucleosome loss at genes induced in stress. Whereas, repressed genes seems to possess Mediator and RNAP2 in an inactive form which could be the mechanism of repression and a way to activate these genes immediate after stress.