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 #
5R01GM059055-12
Application #
8217118
Study Section
Molecular Genetics B Study Section (MGB)
Program Officer
Sledjeski, Darren D
Project Start
2000-02-01
Project End
2013-01-31
Budget Start
2012-02-01
Budget End
2013-01-31
Support Year
12
Fiscal Year
2012
Total Cost
$302,003
Indirect Cost
$93,732
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
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) 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
Lai, William K M; Pugh, B Franklin (2017) Genome-wide uniformity of human 'open' pre-initiation complexes. Genome Res 27:15-26
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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