Peter J. Harte, PhD
Professor, Genetics and Genome Sciencespjh3@case.edu 216.368.6417 (o) 216.368.3432 (f)
Member, Molecular Oncology Program
We are interested in the molecular mechanisms underlying regulation of homeotic gene expression during Drosophila development. The homeotic genes encode a family of transcription factors that act as key determinants of embryonic cell fates. Each is expressed in a different region of the embryo, programming the cells in which it is expressed to follow a specific developmental pathway.
We are interested in how the spatially restricted patterns of homeotic gene expression are established and stably maintained throughout development.
We are currently investigating two proteins, an activator and a repressor, required for maintenance, which most likely involves stable alterations in chromatin structure.
The Trithorax protein is required to sustain normal levels of transcription of homeotic genes throughout development. It contains a novel DNA binding domain and several other novel motifs found in other proteins involved in remodeling chromatin structure.
We are characterizing TRX binding sites in the homeotic genes, identifying proteins that interact with TRX, and investigating its mechanism of action in vivo and in vitro. The ESC protein is a novel highly conserved repressor required for maintaining transcriptional silencing of homeotic genes in cells outside their normal expression domains. ESC binds to chromosomes, but does not bind to DNA directly.
We are investigating how ESC is recruited to its target genes, its interactions with proteins that might mediate its recruitment, including other proteins involved in silencing homeotic genes, and whether ESC promotes silencing by stably altering chromatin structure once bound.