DNA Sequence-Encoded Nucleosome Positioning, and Gene Regulation

Northwestern University At Chicago, Evanston IL

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Abstract

The detailed locations of nucleosomes along the genomic DNA are major determinants of gene expression, n simple eul<aryotes, the genomic DNA sequence explicitly encodes the majority of the in vivo nucleosome organization and thereby regulates the competition of nucleosomes and gene regulatory proteins, facilitating many specific chromosome functions. In higher organisms, however, the extent to which the genomic sequence encodes nucleosome locations has been questioned and is not known. Moreover, higher organisms have differing nucleosome concentrations in differing cell types, with unclear ramifications for nucleosome positioning and chromosome function. This project will obtain needed data and develop quantitative predictive models for nucleosome locations, chromatin superstructures, nucleosome-factor competition, and gene expression levels, in development and cancer, using mouse and human cell line systems.