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New mechanism for essential genome-wide gene silencing identified

Most of the time in most cells of the body, the great majority of genes are silenced, locked away within the compacted but orderly material that makes up chromosomes. Estimates are that only about 10 percent of the roughly 25,000 genes in the human genome are activated, or "on," at any given time in a particular cell the default setting for most genes is "off," or repressed.

Reliable gene silencing is vital to the health of an organism. Improperly activated genes can and do lead to cancer, for example. Gene silencing is also thought to protect the genome from viruses and other potentially damaging entities, thus preserving genetic integrity.

In a new study, researchers at The Wistar Institute and colleagues have identified an important new global mechanism for this essential gene silencing, or gene repression. A report on the findings appears in the April 15 issue of Genes & Development.

"We've discovered what looks to be an evolutionarily ancient mechanism for broadly repressing and protecting the genome," says Shelley L. Berger, Ph.D., the Hilary Koprowski Professor at The Wistar Institute and senior author on the study. "We believe it to be the first identified mechanism of its kind."

The new mechanism centers on histones, relatively small proteins around which DNA is coiled to create structures called nucleosomes. Compact strings of nucleosomes, then, form into chromatin, the substructure of chromosomes.

In the study, conducted in a type of yeast called Saccharomyces cerevisiae, the scientists showed that a protein called SUMO binds to histones and acts to repress transcription of genes, and it does so at many different sites across the genome. While several other histone-related mechanisms have been identified for activating genes in yeast, this is the first one recognized as repressing gene transcription.

The finding is significant because gene-regulation strategies first observed yeast and other lower-order o
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Contact: Franklin Hoke
hoke@wistar.org
215-898-3716
The Wistar Institute
14-Apr-2006


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