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Molecular Genetics of the Bithorax Complex

$339,424R01FY2014GMNIH

Harvard Medical School, Boston MA

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Abstract

DESCRIPTION (provided by applicant): The bithorax complex in the fruit fly, Drosophila melanogaster, is a cluster of genes that determines the identities the body segments of the fly. It includes multiple regulatory regions, one for each body segment, which are arranged on the chromosome in the order of the segments that they affect. The genes, and their chromosomal order, are conserved between flies and humans. We wish to understand how the regulatory regions become appropriately activated or repressed in each body segment. The repressed state is imposed by a several genes collectively called the Polycomb Group; these genes are also well conserved. In both flies and mammals, they regulate a large number of other genes required in specific cell types. We are able to isolate nuclei from individual segments of the fly embryo, and map chromosomal proteins across the bithorax complex in each segment. We focus on the Polycomb Group proteins, and on modifications to the histone proteins covering the DNA. We will introduce mutations in critical DNA elements, to learn how large domains of Polycomb-mediated repression are established and maintained.

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