Grant: Discovery Grants Program - Individual

Genomic imprinting, the epigenetic marking of the genomes according to their parental origin, has been documented in a wide variety of animals and plants including mammals, higher and lower vascular plants, fish and insects. Among the latter is the model organism Drosophila melanogaster. During the tenure of my last two NSERC discovery grants my research group identified genes that regulate imprinting. These genes fall into different classes: those acting in the somatic cells maintain the imprint and those acting in the germ-line erase and then re-set the imprint from previous generations. Among the genes we identified were a number of highly conserved chromatin proteins that modify histones or form higher order chromatin structures, some of these have recently been found to play a role in mammalian imprinting. In this application, I propose to identify the last, and most intractable, class of imprint regulatory genes - those that erase the imprint. I also propose to extend our initial work investigating the evolutionary conservation of imprinting by looking for evidence of imprinting in previously un-investigated non-model organisms. The correct imprinting of early acting genes is vital for normal human development, and as a result a number of diseases arise from defective imprinting. Likewise, disrupted imprinting contributes to the poor viability of cloned animals and animals generated through assisted reproductive technology. As is true in mammals, Drosophila imprints its genome, however, in only non-essential genes are imprinted so that the imprinting process can be more readily genetically manipulated. Coupled with sophisticated genetic tools, this makes Drosophila a good model system in which to identify the molecular mechanism of imprinting.