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Novel method conceived, to achieve genome-wide gene silencing.

Most cells in our body have a great number of genes that are safely ensconced in the systematic pattern of chromosomes. According to estimates, only 10% of the // nearly 25,000 genes in the human genome are in an alert state in a particular cell, the rest are only latent and in a dormant state.

This trait of genes, called gene silencing is crucial to an organism’s health. Gene silencing offers a protective cover for the genome from viruses, and even cancer, and is a big step towards maintaining genetic integrity.

Researchers at The Wistar Institute and colleagues have discovered a novel way for achieving gene silencing, or gene repression. A report on the findings appears in the April 15 issue of Genes & Development.

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

Small proteins called Histones, around which the DNA is entwined, creates structures called nucleosomes. Compact strings of nucleosomes, then, form into chromatin, the substructure of chromosomes.

Researchers conducted the study with a type of yeast called Saccharomyces cerevisiae, the scientists showed that a protein called SUMO holds on to the 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 assumes great importance in gene-regulation methods. According to Berger, "In our experiments, we saw SUMO binding to histones across the genome, suggesting that if this mechanism went wrong, it could have a dramatic effect. We know, for example, that histones are important in a number of cancers, and SUMO may be a significant part of that."


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