Studies of enhancer action in trans in Drosophila

Harvard University (Medical School), Boston MA

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Abstract

[unreadable] DESCRIPTION (provided by applicant): The goal of this research is to understand how enhancers interact with their appropriate promoters. Because promiscuous activity of enhancers can lead to inappropriate expression of regulatory and developmental genes leading to disease, it is important that we understand how enhancers normally identify their relevant transcriptional units. To approach this question, we will use Drosophila to study a process called transvection, wherein an enhancer on one chromosome can activate a homolog in trans when the two sequences are allowed to pair. Although transvection has been observed for several genes, it is unknown whether the ability to activate genes on a homologous chromosome is a general property of enhancers. We will address this question by testing well-characterized enhancer elements for their ability to support transvection. A second goal of the research is to identify other genes that help regulate transvection. Thus, we will take advantage of the powerful genetics tools afforded by Drosophila and screen the genome for mutations that fail to support transvection. Since transvection requires that homologous chromosomes be paired, these studies should also shed light on other homology-dependent processes, such as imprinting and homology-dependent gene silencing, which have been implicated in genetic diseases and potential gene therapeutics respectively. [unreadable] [unreadable]