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Cells take risks with their identities

CAMBRIDGE, Mass. (July 11, 2007) -- Biologists have long thought that a simple on/off switch controls most genes in human cells. Flip the switch and a cell starts or stops producing a particular protein. But new evidence suggests that this model is too simple and that our genes are more ready for action than previously thought.

Scientists in the lab of Whitehead Member Richard Young have discovered that many human genes hover between on and off in any given cell. According to the study, which appears online in Cell on July 12, these genes begin making RNA templates for proteinsa process termed transcriptionbut fail to finish. The templates never materialize, and the proteins never appear.

Surprisingly, about one-third of our genes, including all the regulators of cell identity, fall into this new class, says Young, who is also an MIT professor of biology. It seems awfully risky for an adult cell to leave genes primed that could change its identity.

The human body comprises more than 200 types of cells. Each cell contains the same complete set of genes, but expresses only a unique fraction of them, churning out proteins that make it a nerve or skin or white blood cell. Scientists have known for years that a cell hides the genes it doesnt need by coiling the dormant DNA tightly around protein spools called histones. The new study, however, suggests that DNA packaging stays loose at the beginning of many inactive genes, contrary to textbook models.

Whitehead postdoctoral researchers Matthew Guenther and Stuart Levine screened the entire human genome for a chemical signaturea landmarkthat corresponds with this looser DNA packaging configuration and thus with transcription initiation. They worked with embryonic stem cells, liver cells and white blood cells.

We expected to find the landmark on 30 to 40 percent of the genes because thats how many are active in each cell, Guenther says. We were shocked when it showed up o
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Contact: Alyssa Kneller
kneller@wi.mit.edu
617-258-6851
Whitehead Institute for Biomedical Research
12-Jul-2007


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