The regulation of gene transcription is fundamental to the existence of complex multicellular organisms, and errors in this regulation lead to abnormal cell function and disease. Despite the availability of the complete human genome sequence, we still know far too little about the sequence-specific interactions of regulatory proteins with particular genetic loci that control and regulate gene expression. The goal of the Wisconsin Center of Excellence in Genomics Science is to invent novel technologies that will characterize DNA-protein interactions on a genome-wide scale. This technology will allow us to monitor how protein binding changes over time during biological processes or development, and define the genetic components of disease. This knowledge will further help our quest to understand and functionalize our genome, and allow for new approaches in therapeutics and personalized medicine.
Currently existing methodologies are not scaled to examine DNA-protein interactions on a genome-wide scale. Some methods focus on the interactions of individual DNA sequences and binding proteins (e.g. EMSA and DNAse footprinting), but fail to provide information on the in vivo nature of the DNA-protein interactions (which is critical to understanding the regulatory mechanism and dynamics). Other methods research the interaction of an individual protein with DNA (ChIP), but these require specific antibodies for all proteins of interest.
There is a desperate need for new technologies to allow the comprehensive parallel analysis of all DNA-protein interactions without prior knowledge or assumptions.
The Wisconsin CEGS, funded by the National Human Genome Research Institute at the National Institutes of Health, addresses this need in a new collaborative effort that develops a toolbox that can be used to better understand the relationships between changes in DNA-protein interactions and the underlying complex machinery controlling genes.
Results
We have recently developed a novel breakthrough methodology called GENECAPP, for Global ExoNuclease-based Enrichment of Chromatin-Associated Proteins for Proteomics. For details on our initial technology development and application, see our Research Page or our Publications.
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