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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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) Genome-wide structure and organization of eukaryotic pre-initiation complexes. Nature 483:295-301
Batta, Kiran; Zhang, Zhenhai; Yen, Kuangyu et al. (2011) Genome-wide function of H2B ubiquitylation in promoter and genic regions. Genes Dev 25:2254-65
Venters, Bryan J; Irvin, Jordan D; Gramlich, Paul et al. (2011) Genome-wide transcriptional dependence on conserved regions of Mot1. Mol Cell Biol 31:2253-61
Sen, Payel; Ghosh, Sujana; Pugh, B Franklin et al. (2011) A new, highly conserved domain in Swi2/Snf2 is required for SWI/SNF remodeling. Nucleic Acids Res 39:9155-66
Huisinga, Kathryn L; Pugh, B Franklin (2007) A TATA binding protein regulatory network that governs transcription complex assembly. Genome Biol 8:R46
Durant, Melissa; Pugh, B Franklin (2007) NuA4-directed chromatin transactions throughout the Saccharomyces cerevisiae genome. Mol Cell Biol 27:5327-35
Irvin, Jordan D; Pugh, B Franklin (2006) Genome-wide transcriptional dependence on TAF1 functional domains. J Biol Chem 281:6404-12
Durant, Melissa; Pugh, B Franklin (2006) Genome-wide relationships between TAF1 and histone acetyltransferases in Saccharomyces cerevisiae. Mol Cell Biol 26:2791-802
Ioshikhes, Ilya P; Albert, Istvan; Zanton, Sara J et al. (2006) Nucleosome positions predicted through comparative genomics. Nat Genet 38:1210-5

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