SGER: Developmental Genomics: Systematic Analysis of Transcription Factor DNA-Binding Specificities

University Of California-San Diego, La Jolla CA

Investigators

Abstract

POSAKONY The availability of complete genomic sequence data for many organisms will greatly accelerate unraveling the transcriptional regulatory network underlying their development. However, this effort, what might be termed "developmental genomics", is currently seriously hampered by the lack of systematic determinations of the DNA-binding specificities of most transcription factors. The project seeks to address this deficiency, and will consist of three principal phases: (1) Express in, and purify from, bacteria a selected set of transcription factor fusion proteins. (2) Determine the DNA-binding specificity of each protein by an affinity chromatography random oligonucleotide selection method. (3) Analyze and post binding site data on suitable Web sites (e.g., TRANSFAC) in the form of position weight matrices; make fusion protein plasmids freely available. Only part of the scientific and public benefit of having complete DNA sequences for various organisms, including both humans and animal models such as mice and fruit flies, will derive from knowing all of the proteins these species can make. It will also be extremely valuable to identify and study the regulatory sequences associated with each gene that control the times and tissues in which each protein is produced. This research will contribute strongly to this effort, by determining the specific DNA sites at which key regulatory proteins interact with the genes they control.