Man and mouse share genome structures

In the most detailed large-scale study to date of the proteins that package DNA, researchers have mapped a family of switches that turn genes on and off. Their findings may help scientists understand regulatory mechanisms underlying cancer and human development.

The research team includes first author Bradley Bernstein, recipient of a Howard Hughes Medical Institute (HHMI) physician postdoctoral fellowship who works in the Harvard University laboratory of HHMI investigator Stuart L. Schreiber. Other co-authors are from the Broad Institute of MIT and Harvard, and Affymetrix. Their findings are published in the January 28, 2005 issue of Cell.

"Now that the human genome has been sequenced, it is vital to learn how the genome is translated to make living cells and organisms, and how we can use that information to improve human health," said Bernstein, who is an instructor of pathology at Brigham & Women's Hospital and Harvard Medical School. "Every one of our cells has the same genome, yet is completely different. Muscle cells are different from neurons. They are different because different genes are on."

Many scientists believe changes in the regulatory scaffolding surrounding the genome may be as important as changes in the genome itself in causing diseases such as cancer.

This regulatory structure, called chromatin, is a key regulator of gene expression in healthy and diseased cells, Bernstein said. Chromatin is composed of DNA spooled around bundles of histone proteins, and resembles a chain of beads which is then compressed into a working chromosome. Chemical tags placed on the histones alter the way chromatin is organized, thus allowing the right combination of genes to be turned on.

In their study, the researchers analyzed the chromatin structure of the two shortest human chromosomes, numbers 21 and 22, containing about two percent of the human genome. They also sampled additional regions in both the human and mouse gen

Contact: Jennifer Donovan
Howard Hughes Medical Institute

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