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. ? ?

Agency
National Institute of Health (NIH)
Institute
National Institute of General Medical Sciences (NIGMS)
Type
Postdoctoral Individual National Research Service Award (F32)
Project #
1F32GM067460-01
Application #
6585016
Study Section
Special Emphasis Panel (ZRG1-F08 (20))
Program Officer
Tompkins, Laurie
Project Start
2003-02-01
Project End
Budget Start
2003-02-01
Budget End
2004-01-31
Support Year
1
Fiscal Year
2003
Total Cost
$41,608
Indirect Cost
Name
Harvard University
Department
Genetics
Type
Schools of Medicine
DUNS #
047006379
City
Boston
State
MA
Country
United States
Zip Code
02115
Griffin, Ruth; Sustar, Anne; Bonvin, Marianne et al. (2009) The twin spot generator for differential Drosophila lineage analysis. Nat Methods 6:600-2
Bateman, Jack R; Wu, C-ting (2008) A simple polymerase chain reaction-based method for the construction of recombinase-mediated cassette exchange donor vectors. Genetics 180:1763-6
Bateman, Jack R; Wu, C-ting (2008) A genomewide survey argues that every zygotic gene product is dispensable for the initiation of somatic homolog pairing in Drosophila. Genetics 180:1329-42
Williams, Benjamin R; Bateman, Jack R; Novikov, Natasha D et al. (2007) Disruption of topoisomerase II perturbs pairing in drosophila cell culture. Genetics 177:31-46
Bateman, Jack R; Lee, Anne M; Wu, C-ting (2006) Site-specific transformation of Drosophila via phiC31 integrase-mediated cassette exchange. Genetics 173:769-77