Franklin and Marshall College
University of California, Berkeley
- 1/1/2002 Sci/Tech Web Award, Scientific American
Identification of the cis-regulatory elements that control coordinate gene expression is one of the longstanding goals of molecular biology. We have developed an integrated methodology and accompanying algorithms, including EvoPrinter and a suite of web-accessed search algorithms, cis-Decoder, that identifies functionally related cis-regulatory enhancers. For this analysis we have generated a Drosophila genome-wide database of conserved DNA consisting of greater than 100,000 conserved sequence clusters (CSCs) derived from EvoPrints spanning over 90% of the genome. cis-Decoder first identifies conserved repeat elements within an input enhancer and then searches the database for CSCs that score highly against the input CSC. Scoring is based on shared repeats as well as uniquely shared matches, and includes measures of the balance of shared elements, a diagnostic that has proven to be useful in predicting cis-regulatory function.
To demonstrate the utility of these tools, a temporally-restricted CNS neuroblast enhancer, characterized in our analysis of regulation of the temporal determinant castor, was used to identify other functionally related enhancers and analyze their structural organization.cis-Decoder reveals that co-regulating enhancers consist of combinations of overlapping shared sequence elements, providing insights into the mode of integration of multiple regulating transcription factors. The database and accompanying algorithms should prove useful in the discovery and analysis of enhancers involved in any developmental process.
For the last seventeen years I have maintained the Web resource entitled The Interactive Fly: A Cyberspace Guide to Drosophila Development and metazoan evolution. Drosophila is a good starting place from which to design an interactive model of development, and cyberspace is the made-to-order medium. The Interactive Fly is used at every level of study, including high school, college, graduate school and as a reference for researchers. It has also been used by programmers to develop methods of machine reading of biology text.
- Brody T, Yavatkar AS, Kuzin A, Kundu M, Tyson LJ, Ross J, Lin TY, Lee CH, Awasaki T, Lee T, Odenwald WF. (2012) Use of a Drosophila genome-wide conserved sequence database to identify functionally related cis-regulatory enhancers, Dev Dyn. 241(1), 169-89. Full Text/Abstract
- Kuzin A, Kundu M, Ross J, Koizumi K, Brody T, Odenwald WF. (2012) The cis-regulatory dynamics of the Drosophila CNS determinant castor are controlled by multiple sub-pattern enhancers, Gene Expr Patterns 12(7-8), 261-72. Full Text/Abstract
- Kuzin A, Kundu M, Brody T, Odenwald WF. (2011) Functional analysis of conserved sequences within a temporally restricted neural precursor cell enhancer, Mech Dev. 128(3-4), 165-77. Full Text/Abstract
- Kuzin A, Kundu M, Ekatomatis A, Brody T, Odenwald WF. (2009) Conserved sequence block clustering and flanking inter-cluster flexibility delineate enhancers that regulate nerfin-1 expression during Drosophila CNS development, Gene Expr Patterns 9, 65-72. Full Text/Abstract
- Yavatkar AS, Lin Y, Ross J, Fann Y, Brody T, Odenwald WF. (2008) Rapid detection and curation of conserved DNA via enhanced-BLAT and EvoPrinterHD analysis., BMC Genomics 9, 106. Full Text/Abstract
All Selected Publications