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.

Public Health Relevance

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.

National Institute of Health (NIH)
National Institute of General Medical Sciences (NIGMS)
Research Project (R01)
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Study Section
Molecular Genetics B Study Section (MGB)
Program Officer
Sledjeski, Darren D
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Pennsylvania State University
Schools of Arts and Sciences
University Park
United States
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Lai, William K M; Pugh, B Franklin (2016) Genome-wide uniformity of human 'open' pre-initiation complexes. Genome Res :
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
Reja, Rohit; Vinayachandran, Vinesh; Ghosh, Sujana et al. (2015) Molecular mechanisms of ribosomal protein gene coregulation. Genes Dev 29:1942-54
Wang, Shu; Chen, Xiangyun Amy; Hu, Jing et al. (2015) ATF4 Gene Network Mediates Cellular Response to the Anticancer PAD Inhibitor YW3-56 in Triple-Negative Breast Cancer Cells. Mol Cancer Ther 14:877-88
Schneider, Maren; Hellerschmied, Doris; Schubert, Tobias et al. (2015) The Nuclear Pore-Associated TREX-2 Complex Employs Mediator to Regulate Gene Expression. Cell 162:1016-28
Venters, Bryan J; Pugh, B Franklin (2013) Genomic organization of human transcription initiation complexes. Nature 502:53-8
Rhee, Ho Sung; Pugh, B Franklin (2012) ChIP-exo method for identifying genomic location of DNA-binding proteins with near-single-nucleotide accuracy. Curr Protoc Mol Biol Chapter 21:Unit 21.24
Rhee, Ho Sung; Pugh, B Franklin (2012) Genome-wide structure and organization of eukaryotic pre-initiation complexes. Nature 483:295-301

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