Elucidating mechanisms of enhancer-promoter specificity

Harvard University (Medical School), Boston MA

Investigators

Abstract

To understand better the mechanisms that control enhancer-promoter specificity we will study transvection, a genetic phenomenon in Drosophila in which one allele of a gene is able to affect the expression of its homologue allele in a pairing-dependent manner. At the Drosophila yellow gene, transvection can occur when enhancers from one allele activate transcription, in trans, from the promoter of the other allele on the homologous chromosome. As these enhancers normally function only in cis, yellow transvection represents a change in enhancer-promoter specificity from a cis- to a trans-specific state. Our goals are twofold: 1) To study the mechanisms that allow enhancers to act in trans; 2) To identify the trans-acting factors that mediate transvection. As the few candidate factors thought to modulate transvection have highly conserved vertebrate counterparts known to function as proto-oncogenes (e.g. bmi-1) and tumor suppressor genes (e.g. mel-18), information gleaned from these studies will likely be of direct relevance to an understanding of cancer in humans.