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Novel enzyme offers new look at male hormone regulation

CHAPEL HILL For the second time in less than a year, University of North Carolina at Chapel Hill scientists have purified a novel protein and have shown it can alter gene activity by reversing a molecular modification previously thought permanent.

The findings, published today (May 5) in the journal Cell, also show that the new protein plays a role in gene activation mediated by androgen receptor, a protein that responds to androgen hormones. In this regard, the novel protein may figure in the development of prostate cancer.

Androgens, particularly testosterone and dihydrotestosterone, determine male secondary sex characteristics and stimulate prostate cell growth. Lowering androgen levels usually can make prostate cancers shrink or grow more slowly.

In the study, the researchers said the new protein called JHDM2A, like the protein they reported on in the journal Nature in December 2005, is able to remove a methyl group from histone H3, one of four histone proteins bound to all genes.

"Human genes are so tightly compact within the nucleus that if the DNA of a single cell were unwound and stretched, it would be a line of about two meters in length. Histones are necessary to package the DNA so that it fits inside a cell's nucleus," said senior author Dr. Yi Zhang, professor of biochemistry and biophysics at UNC's School of Medicine and the university's first Howard Hughes Medical Institute investigator.

Zhang also is a member of the UNC Lineberger Comprehensive Cancer Center.

Because histones are so intimately associated with DNA, even slight chemical alterations of these proteins can have profound effects on nearby genes. Depending on their precise location and how many methyl groups are added, the presence of alterations can either turn on or turn off a gene.

In the study, Zhang learned that the JHDM2A specifically removes methyl-groups from lysine 9 of histone H3.

"The important thing is that H3
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Contact: Leslie H. Lang
llang@med.unc.edu
919-843-9687
University of North Carolina School of Medicine
5-May-2006


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