Study provides new insights into emerging theory of gene regulation

PHILADELPHIA -- With the full sequence of the human genome now in hand, scientists are turning renewed attention to the molecular processes that regulate the genes encoded by DNA. Estimates are that only a tenth of all genes are expressed at any given time. What controls when and where genes are activated?

Increasingly, researchers believe that the mechanisms that govern gene activity themselves resemble a complicated non-DNA code an intricate pattern of activity among the molecules that package and control access to the DNA. They suspect that the coordinated interplay of a number of specific enzymes is required to turn on a particular gene.

Now, in a new study using the techniques of structural biology, investigators at The Wistar Institute have shown in detail how two enzymes work together to activate a specific gene by loosening, at that gene's location, the compact coils of DNA and packaging proteins called chromatin. The findings bolster the emerging theory that something like a code is responsible for orchestrating genetic activity. A report on the research appears in the August issue of Molecular Cell, published August 28.

"This is the first time we've understood the precise mechanism of how two specific modifications to the DNA packaging proteins interact synergistically to promote the expression of a particular gene," says Ronen Marmorstein, Ph.D., a professor in the Gene Expression and Regulation Program at Wistar and senior author on the study.

Most of the time, the great majority of genes are silenced, locked away within the packaging proteins of chromatin. For a given gene to be activated when needed, the chromatin must be opened at that gene's location on the DNA, and that location only, to make the gene physically accessible for transcription. Histone proteins play a key role in this process.

Histones are relatively small proteins around which DNA is coiled to create structures called nucleosomes. Compact strin

Contact: Franklin Hoke
The Wistar Institute

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