Organisms are constantly faced with environmental extremes, involving temperature, starvation, radiation and harmful chemicals. Inducible genes have evolved to respond to these challenges. Organisms are also faced with day-to-day housekeeping tasks, such as synthesizing biomolecules. Recent studies in the budding yeast Saccharomyces cerevisiae suggest that eukaryotes balance housekeeping and stress-response needs through two distinct transcriptional regulatory pathways, represented by two related components of the transcription machinery, TFIID and SAGA, respectively. Knowing whether a gene is primarily regulated by TFIID or SAGA provides enormous predictive insight into its regulation by other transcriptional regulators, and its broader cellular role. Many aspects of this dual pathway remain to be elucidated. The TFIID/SAGA classification has not been conducted under a wide range of conditions that put the genome through its full range of expression, which is necessary for appropriate classification of all genes. While SAGA as been implicated in stress-induced gene expression, it is not known whether its action protects cells from stress. Genes repressed by stress utilize TFIID rather than SAGA, but little is known about what promoter elements control this process. The TATA box has also been implicated in the stress-response. Many TATA-less genes have a conserved TATA box far upstream of its normal location. It's potential involvement in gene regulation remains unknown. To address these problems which are germane to an organism's stress-response and the potential to develop therapeutic agents that heighten the stress response, the following specific aims are proposed: 1) Classify the TFIID/SAGA-dependence of all yeast genes under a wide range of environmental stresses. 2) Determine whether SAGA and/or TFIID provide stress protection. 3) Identify the promoter determinants of stressdirected gene repression. 4) Assess the function of far-upstream TATA boxes. ? ?
| Vinayachandran, Vinesh; Reja, Rohit; Rossi, Matthew J et al. (2018) Widespread and precise reprogramming of yeast protein-genome interactions in response to heat shock. Genome Res : |
| Yamada, Naomi; Lai, William K M; Farrell, Nina et al. (2018) Characterizing protein-DNA binding event subtypes in ChIP-exo data. Bioinformatics : |
| Rossi, Matthew J; Lai, William K M; Pugh, B Franklin (2018) Simplified ChIP-exo assays. Nat Commun 9:2842 |
| Niu, Ben; Coslo, Denise M; Bataille, Alain R et al. (2018) In vivo genome-wide binding interactions of mouse and human constitutive androstane receptors reveal novel gene targets. Nucleic Acids Res 46:8385-8403 |
| Rossi, Matthew J; Lai, William K M; Pugh, B Franklin (2018) Genome-wide determinants of sequence-specific DNA binding of general regulatory factors. Genome Res 28:497-508 |
| Miller, Jason E; Zhang, Liye; Jiang, Haoyang et al. (2018) Genome-Wide Mapping of Decay Factor-mRNA Interactions in Yeast Identifies Nutrient-Responsive Transcripts as Targets of the Deadenylase Ccr4. G3 (Bethesda) 8:315-330 |
| Mahony, Shaun; Pugh, B Franklin (2015) Protein-DNA binding in high-resolution. Crit Rev Biochem Mol Biol 50:269-83 |
| Chang, Gue Su; Chen, Xiangyun Amy; Park, Bongsoo et al. (2014) A comprehensive and high-resolution genome-wide response of p53 to stress. Cell Rep 8:514-27 |
| Nakahashi, Hirotaka; Kieffer Kwon, Kyong-Rim; Resch, Wolfgang et al. (2013) A genome-wide map of CTCF multivalency redefines the CTCF code. Cell Rep 3:1678-1689 |
| Li, Jian; Liu, Yingyun; Rhee, Ho Sung et al. (2013) Kinetic competition between elongation rate and binding of NELF controls promoter-proximal pausing. Mol Cell 50:711-22 |
Showing the most recent 10 out of 17 publications
