Protein discovery tied to DNA master switch

(Embargoed) CHAPEL HILL - A new cellular protein discovered by scientists at the University of North Carolina at Chapel Hill appears to be a crucial molecular component of a master switch that turns genes on and off.

The new molecule may prove critical to the regulation of gene expression. If so, it could eventually lead to new treatments for diseases and provide information vital to research aimed at using stem cells to generate organs.

The discovery of the new molecule, SET7, was headed by Dr. Yi Zhang, assistant professor of biochemistry at UNC-CH School of Medicine and a member of the UNC Lineberger Comprehensive Cancer Center. A report of the research is published in the December 21 issue of the journal Molecular Cell.

All gene expression must be tightly controlled, Zhang said. "When we talk about genes, we're talking about DNA in the cell nucleus that's complexed with several basic proteins called histones. The basic structure is like 'beads on a string' which can be further packaged into a high order structure called chromatin," he explained.

"This chromatin packaging allows for efficient storage of genetic information. But it also impedes access to DNA by transcription factors, proteins that regulate gene expression."

Zhang and his colleagues believe their discovery to be part of the mechanism that dynamically changes the chromatin structure, its loosening or tightening. They focused their attention on a particular covalent modification -- methylation, addition of a methyl group to lysine, one of the amino acids that comprise the tail domain of the histone molecules.

Why lysine? Because recent research had linked gene silencing, or deactivation, to methylation of a particular lysine site (lysine 9) on the tail of the histone H3.

As it turns out, modifications of amino acids by methylation mainly occur on lysine. "We've known for three decades that histone can be methylated, but nobody knew the

Contact: Leslie Lang
University of North Carolina School of Medicine

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