Wistar study offers new support for a 'histone code' theory of gene regulation

PHILADELPHIA - A new study by researchers at The Wistar Institute provides important experimental data to support a novel theory of gene regulation. The theory holds that coordinated patterns of modifications to DNA-packaging proteins called histones may be a key factor in turning specific genes on or off.

The proposed system of gene control has been termed a kind of "histone code" by one researcher and may govern most gene activity. Understanding the system could well prove crucial to researchers exploring cancer, developmental disorders, and other disease processes that hinge on gene control gone awry.

In their study, the Wistar scientists identified an enzyme that works in concert with another enzyme to modify a histone, triggering the transcription of a particular gene in yeast. The findings represent one of the first times that two modifications of a histone, one dependent on the other, have been shown to be necessary for a gene's activation. A report on the work appears in the August 10 issue of Science.

"The linking of this pair of histone modifications to the transcription of a gene strongly supports the notion that a kind of intricate interplay among such alterations - a code, if you will - may be controlling the greater part of gene activity," says Shelley L. Berger, Ph.D., an associate professor and senior author on the study. "Scientists are just beginning to explore this system of gene regulation. Already, however, it looks as though it may of comparable importance to the discovery some years ago of activator and repressor molecules that bind directly to DNA to turn genes on or off."

Estimates are that only a tenth of all human genes are expressed at any given time. Most of the time, the great majority of genes are silenced, locked away within a complex packaging scheme of proteins called chromatin. For a given gene to be activated when needed, the chromatin must be opened at that location on the DNA, and that location o

Contact: Franklin Hoke
The Wistar Institute

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