The research findings, published Aug. 29 in the science journal Molecular Cell, add important knowledge to the understanding of epigenetic signals. These chemical signals affect the modulation of gene expression - activation or repression - throughout the genome.

Studies at UNC and elsewhere have shown that epigenetic phenomena underpin the shutting down of one copy of the X chromosome occurring in female mammals, and parental "imprinting" - in which a gene's activity depends on whether it's inherited from the mother or father. During development, the expression of whole sets of genes must be repressed, or silenced, after their proteins set the body pattern.

One such epigenetic event is histone methylation, the addition of one or more methyl groups to lysine, one of the amino acids that make up the "tail" domain of histone proteins. Within the cell nucleus, spiraling strands of DNA are wrapped tightly around four core histone proteins and then fold to form a densely packed structure called chromatin. This complex of nucleic acids and proteins packages DNA into higher order structures, ultimately forming a chromosome.

The chemical modification of histone tails can alter chromatin structure, loosening or tightening it, which in turn influences the expression of adjacent genes. In the journal article, a study team led by Dr. Yi Zhang, assistant professor of biochemistry and biophysics in UNC's School of Medicine and a member of UNC's Lineberger Comprehensive Cancer Center, reported having identified for the first time a protein that directly regulates lysine methylation on the core histone protein, H3, in a way that represses gene activity.

"We have found the first molecule, the first gene product, that can regulate methylation," Zhang said.

In earlier research,
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Contact: Leslie Lang
llang@med.unc.edu
919-843-9687
University of North Carolina School of Medicine
2-Sep-2003