Study provides new insights into emerging theory of gene regulation

gs of nucleosomes, then, form into chromatin, a substructure of chromosomes. When the DNA is tightly wrapped around the histones, the genes cannot be accessed and their expression is repressed. When the coils of DNA around the histones are loosened, the genes become available for expression, and it is the enzymatic activity governing this process in a specific case that Marmorstein's laboratory was able to illuminate.

Working in yeast, Marmorstein and his colleagues showed that when a kinase enzyme adds a phosphoryl group to a histone molecule at a particular location, it helps a histone acetyltransferase enzyme to add an acetyl group at a second location on the same histone molecule. The acetylation of the histone then is thought to prompt a loosening of the DNA coils around the histone to permit transcription of the gene on that length of DNA.

"Five to ten years ago, most biologists thought that the proteins that package DNA served only to maintain physical order," Marmorstein notes. "It's becoming clear, however, that these non-DNA elements of chromosomal structure dramatically influence gene expression. Proteins are coming on and off the DNA at specific times and locations to trigger the activation of genes."

The so-called "histone code" theory of gene regulation, advanced by C. David Allis, Ph.D., at the University of Virginia, and others, suggests that complex, interdependent modifications to the histones are responsible for controlling gene activity. The new data from the Wistar research team supports this view.

The two lead authors on the Molecular Cell study are Adrienne Clements, Ph.D., at Wistar, and Arienne N. Poux, at Wistar and the University of Pennsylvania. Wan-Sheng Lo, Ph.D., at Wistar, and Lorraine Pillus, at the University of San California, San Diego, are co-authors. Shelley L. Berger, Ph.D., the Hilary Koprowski Professor in the Gene Expression and Regulation Program at Wistar, was a collaborator and co-author on

Contact: Franklin Hoke
The Wistar Institute

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