Human health is highly dependent upon proper gene expression. Understanding how genes are regulated is critical in our understanding how mis-regulation leads to diseases. One major point where genes are regulated is during the assembly of the transcription machinery. This project is focused on understanding the molecular events that govern the assembly of the transcription machinery at promoters. The model system is the budding yeast Saccharomyces cerevisiae, because of its experimental tractability and the mechanistic similarities to assembly of the transcription machinery in humans. The project will assess the extent to which individual transcription regulators are dependent upon other transcriptional regulator for binding to the promoters of all Saccharomyces genes upon induction by heat shock. The project will examine in greater mechanistic details portions of the assembly process that involve the transcription pre-initiation complex. In particular, the interplay between chromatin and two major TBP delivery complexes (TFIID and SAGA) will be investigated. We will apply what we have learned from yeast to ask related but highly directed questions at multi-cellular model systems, with particular emphasis on human cells.
Human health is highly dependent upon the proper functioning of our genes (biological instructions). This project will contribute to a greater understanding of how genes function by determining how the protein machinery that reads genes assembles on a global scale.
| García-Molinero, Varinia; García-Martínez, José; Reja, Rohit et al. (2018) The SAGA/TREX-2 subunit Sus1 binds widely to transcribed genes and affects mRNA turnover globally. Epigenetics Chromatin 11:13 |
| 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 : |
| Lai, William K M; Pugh, B Franklin (2017) Genome-wide uniformity of human 'open' pre-initiation complexes. Genome Res 27:15-26 |
| Lai, William K M; Pugh, B Franklin (2017) Understanding nucleosome dynamics and their links to gene expression and DNA replication. Nat Rev Mol Cell Biol 18:548-562 |
| Rossi, Matthew J; Lai, William K M; Pugh, B Franklin (2017) Correspondence: DNA shape is insufficient to explain binding. Nat Commun 8:15643 |
| Baranello, Laura; Wojtowicz, Damian; Cui, Kairong et al. (2016) RNA Polymerase II Regulates Topoisomerase 1 Activity to Favor Efficient Transcription. Cell 165:357-71 |
| Pugh, B Franklin; Venters, Bryan J (2016) Genomic Organization of Human Transcription Initiation Complexes. PLoS One 11:e0149339 |
| Han, G Celine; Vinayachandran, Vinesh; Bataille, Alain R et al. (2016) Genome-Wide Organization of GATA1 and TAL1 Determined at High Resolution. Mol Cell Biol 36:157-72 |
| Jeronimo, Célia; Langelier, Marie-France; Bataille, Alain R et al. (2016) Tail and Kinase Modules Differently Regulate Core Mediator Recruitment and Function In Vivo. Mol Cell 64:455-466 |
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