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Study suggests new view of gene activation as a dynamic process

PHILADELPHIA -- With the sequence of the human genome largely in hand and the majority of genes now available for study, scientists have increasingly turned their attention to better understanding the process of gene regulation. How is a gene turned on? How is a gene turned off? Estimates are that only one in ten genes is active in a given cell at a given time, so these questions are biologically significant. And in many ways, health turns on the appropriate and reliable control of genes. An array of disease conditions can arise if normal gene regulation is perturbed for any reason.

In the case of gene activation, past studies have revealed that specific molecular additions to DNA-packaging proteins called histones are critical to the process. A number of histones are generally involved in the packaging of a single gene, and the picture had emerged of different enzymes adding different molecular groups to different histones to achieve a series of small changes with the collective outcome of turning the gene on. In essence, additions to histones were accumulated until the "on" state was reached.

Now, a new study by researchers at The Wistar Institute reveals the gene-activation process through these molecular modifications to be more dynamic than had been appreciated previously. Specifically, the team's experiments show that, within the process of turning a gene on, the addition of a molecule called ubiquitin is required and, at a different stage of activation, the removal of ubiquitin is also necessary. A sequence of modifications is therefore involved including some that may be reversible, it is now clear. The picture of certain molecular groups being added to histones until the cumulative changes result in gene activation now appears inadequate to explain the process. Instead, a new view that places greater emphasis on the specific order of molecular events within the process of gene activation targeting the histones now seems more informative.
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Contact: Franklin Hoke
hoke@wistar.upenn.edu
215-898-3716
The Wistar Institute
10-Nov-2003


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