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. The project will examine in greater mechanistic details portions of the assembly process that involve recruitment of the TATA binding protein (TBP) to promoters, as TBP is a central linchpin in the assembly process. In particular, the interplay between chromatin and two major TBP delivery complexes (TFIID and SAGA) will be investigated.

Public Health Relevance

Project Narrative 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 gene regulatory proteins work together to read the instructions on a global scale.

Agency
National Institute of Health (NIH)
Institute
National Institute of General Medical Sciences (NIGMS)
Type
Research Project (R01)
Project #
5R01GM059055-10
Application #
7759553
Study Section
Molecular Genetics B Study Section (MGB)
Program Officer
Tompkins, Laurie
Project Start
2000-02-01
Project End
2013-01-31
Budget Start
2010-02-01
Budget End
2011-01-31
Support Year
10
Fiscal Year
2010
Total Cost
$295,072
Indirect Cost
Name
Pennsylvania State University
Department
Biochemistry
Type
Schools of Arts and Sciences
DUNS #
003403953
City
University Park
State
PA
Country
United States
Zip Code
16802
Lai, William K M; Pugh, B Franklin (2017) Genome-wide uniformity of human 'open' pre-initiation complexes. Genome Res 27:15-26
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
Baranello, Laura; Wojtowicz, Damian; Cui, Kairong et al. (2016) RNA Polymerase II Regulates Topoisomerase 1 Activity to Favor Efficient Transcription. Cell 165:357-71
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
Pugh, B Franklin; Venters, Bryan J (2016) Genomic Organization of Human Transcription Initiation Complexes. PLoS One 11:e0149339
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
Reja, Rohit; Vinayachandran, Vinesh; Ghosh, Sujana et al. (2015) Molecular mechanisms of ribosomal protein gene coregulation. Genes Dev 29:1942-54
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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