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Transcription factors may dictate differences between individuals
Date:3/18/2010

Researchers are only beginning to understand how individual variation in gene regulation can have a lasting impact on one's health and susceptibility to certain diseases. Now, an ambitious survey of the human genome has identified differences in the binding of master regulators called transcription factors to DNA that affect how genes are expressed in different people.

The study, which is published in the March 18, 2010, issue of Science, looked at two common transcription factors. HHMI medical research fellow Maya Kasowski and her colleagues in the laboratory of molecular biologist Michael Snyder at Yale University conducted the work with Jan Korbel at the European Molecular Biology Laboratory. Snyder has since joined the faculty at Stanford University.

Transcription factors account for as much as 10 percent of the coding genome in humans and other organisms. When activated, transcription factors switch on or off hundreds or thousands of genes, a cascade that programs cells to grow or divide. "The activity of transcription factors determines what a cell is doing at any given moment," says Kasowski, who was a medical student at Yale when she received her HHMI medical research fellowship. She has since decided to pursue an M.D./Ph.D. degree.

Despite their large numbers and critical role, many aspects of transcription factor biology remain poorly understood. Until now, no one had looked at whether there was any variability in the targets of transcription factors from one person to the next. The current study found a "number of differences between individuals" in the binding sites of two transcription factors, Snyder says.

Transcription factors bind to the human genome within areas of the genome still viewed as a black boxvast stretches of DNA sequence between known genes. Gradually, biologists have found that much of this DNA performs a vital functionhelping turn genes on and off in specific situations. Some of the r
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Contact: Andrea Widener
widenera@hhmi.org
301-215-8807
Howard Hughes Medical Institute
Source:Eurekalert

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