The budding yeast Saccharomyces cerevisiae is used here as model system to understand genomic mechanisms by which genes are regulated. Changes in the disposition of regulatory factors bound across the genome will be monitored when the genome is reprogrammed. The high resolution ChIP-exo and other related assays will be used to monitor genome-wide binding events at near single-bp resolution. Heat shock will be the primary means by which the genome is rapidly reprogrammed since the immediacy of its effect largely ensures that the responding events are a direct consequence of heat shock sensing. This contrasts with other slower environmental sensing systems, where responses may include indirect effects. The general goal of this proposal is to understand gene co-regulation. The work will focus primarily on two distinct classes of genes: ribosomal protein genes (Aim 1), and heat shock induced genes (Aim 2). By defining which factors bind to responding genes and examining the how relevant factors are positionally organized spatially and temporally, and in the context of mutants that are defective in relevant functions, a deeper mechanistic understanding of gene control is obtained. Since yeast is a model for general eukaryotic systems, including human, related biological concepts and approaches developed in yeast will be applied to human cells (Aim 3). This will provide a streamlined approach towards getting at critical questions in human gene regulation, many of which have been opaque to concept development in the absence of a driving model system.

Public Health Relevance

Yeast is a simple model system for understanding biological systems including humans. Proteins that bind throughout the human genome control the genes that govern human health. Precise identification of where and how these proteins bind in the yeast and human genome and their structural organization will inform us as to the mechanics of their action.

National Institute of Health (NIH)
National Institute of General Medical Sciences (NIGMS)
Research Project (R01)
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Molecular Genetics B Study Section (MGB)
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Sledjeski, Darren D
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Pennsylvania State University
Schools of Arts and Sciences
University Park
United States
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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
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