Technique to Explain Patterns of Gene Regulation

Scientists have developed a technique for identifying control elements that drive the expression of genes in brain cells, which could lead to a better understanding of the pathways behind genetic aberrations that cause diabetes, Parkinson's disease, heart disease, and cancer.

The technique resulted from an effort to characterize a family of genes regulated by the cAMP response binding protein (CREB). This molecule is one of a group of transcription factors that interact with regulatory elements in DNA responsible for increasing or decreasing the level of gene expression in cells.

The technique involves linking DNA from a cell with the transcription factor protein, then isolating the complex through immunoprecipitation. Strips of 21-nucleotide-long DNA are then released from the immunoprecipitated DNA to create genomic signature tags, which are then identified in the international genome database. The method has uncovered about 6,300 regulatory regions that mapped to distinct sites on the genome.

The technique was developed by scientists at the Vollum Institute of Oregon Health & Science University (OHSU, Portland, OR, USA), in collaboration with other scientists at Brookhaven U.S. National Laboratory (Upton, NY, USA) and the State University of New York, Stony Brook (NY, USA). Their multidisciplinary study appears in the December 29, 2004 issue of Cell.

Richard Goodman, M.D., Ph.D., professor of cell and developmental biology at OHSU's School of Medicine and director of the Vollum Institute, calls the new process "the most comprehensive analysis to date in a metazoan system--that is, a multicellular system--of where transcription factors bind to their genomic targets.”

"In the past,” he observed, "it's only been possible to look at a very small part of the genome, but now we can look at the whole thing. It's a big step forward.” Scientists are already utilizing the technique in new research projects.