Regulatory Networks with Chromatin Regulators

Massachusetts Institute Of Technology, Cambridge MA

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Abstract

DESCRIPTION (provided by applicant): We propose to use newly developed computational and experimental technologies to model how chromatin modifying complexes contribute to transcriptional regulation of the yeast genome. Genome-wide location analysis, a powerful technique that identifies the set of genes that are bound by regulatory proteins in living cells, will be used to identify the portions of the yeast genome where each of the known chromatin modifying complexes are associated. At least one representative subunit of each of the yeast chromatin modifying complexes will be epitope-tagged and the genomic location of the chromatin regulator will be determined. We will combine previously obtained knowledge of the genome-wide location of DNA-binding regulators with new genome-wide location information for chromatin modifying complexes along with expression data to develop a model for the combination of regulators that operate at most genes. As part of this model, we will explore if physically proximate genes are influenced by a single chromatin-modifying complex. We have shown that some chromatin modifying complexes are recruited by DNA-binding transcriptional regulators, and that others are recruited through a component of the general transcription apparatus. We will model how each of the chromatin regulators are recruited to most yeast genes and the temporal scope of their action. We will monitor dynamic changes in chromatin regulators in synchronized cells and build a model of the yeast cell cycle transcriptional regulatory network that incorporates information on both DNA-binding regulators and chromatin modifying complexes. We will test key features of the model using cells with mutations in chromatin modifying complexes.