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Molecular partners required for appropriate neuronal gene repression

PHILADELPHIA In their efforts to understand the complex biology of life, scientists often seek to isolate individual elements of the puzzle for study, to break the problem down to a more manageable size. Single genes and molecules are closely analyzed to better understand their specific interactions with other single entities within larger systems.

Sometimes, however, this approach misses important aspects of biology that depend on higher levels of organization. Sometimes putting a few of the pieces back together again reveals new information that would otherwise remain obscured.

A new study by researchers at The Wistar Institute demonstrates this point. Aiming for insights into the intricate biochemistry governing gene regulation, the scientists investigated the activity of a recently discovered enzyme pivotally involved in this process. A report on their findings, which may have long-term implications for treating depression and other psychiatric disorders, was published online by Nature today.

The enzyme's function is to remove methyl groups from histones to modify them in ways that trigger gene repression. Eight histones comprise a nucleosome, and long strings of nucleosomes coil in turn into chromatin, the basic material of chromosomes. In the body's scheme for safely storing genes away until needed, DNA is tightly looped around the histones, kept secure by enzymes similar to the one studied by the Wistar team until made accessible by the activity of related enzymes responsible for gene expression.

What the scientists found was that while the enzyme was able to demethylate its target histone when the pair was in isolation, it was unable to do so when the histone was placed in the more complex and realistic setting of a nucleosome. They then coupled the enzyme with other molecules with which it is known to complex to discover that one of them enabled the enzyme to act upon the histone and is, in fact, required for the enzyme's
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Contact: Franklin Hoke
hoke@wistar.org
215-898-3716
The Wistar Institute
3-Aug-2005


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