Targeting transcription: New insights into turnin...( ANN ARBOR Mich.---The 35000 or so gen...)

So just as coaches tell individual players when to scramble onto the field and when to stay on the bench, molecules called transcription factors prompt particular genes to be active or stay quiet. Transcription factors occur naturally in cells, but researchers have been working to develop artificial transcription factors (ATFs) that can be tailored to regulate particular genes or sets of genes. These molecules can help scientists probe transcription, the first step in the process through which instructions coded in genes are used to produce proteins. And because errors in transcription are linked to diseases ranging from diabetes to cancer, ATFs eventually might also be used to correct those mistakes.

Using a new approach to developing ATFs, University of Michigan assistant professor of chemistry Anna Mapp and coworkers have gained important insights into the workings of gene-activating transcription factors. They recently discovered that the gene-activating power of a transcription factor likely depends on where the factor binds to the cell's transcriptional machinery, as well as on how tightly it binds. Previously, researchers had thought that binding affinity (tightness) was the main determinant of a gene activator's potency. Mapp presented the group's results at the annual meeting of the American Chemical Society in New York today (Sept. 8).

Natural transcription factors typically have two essential parts or modules: a DNA-binding module that homes in on the specific gene to be regulated and a regulatory module that attaches itself to the cell's transcriptional machinery through a key protein-to-protein interaction and activates or represses the gene.

"When we started thinking about making artificial transcription factors, we knew we needed t
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Contact: Nancy Ross-Flanigan
rossflan@umich.edu
734-647-1853
University of Michigan
11-Sep-2003