Epigenetic research uncovers new targets for modification enzymes

A consortium of scientists, led by Albert Jeltsch, professor of Biochemistry at Jacobs University Bremen, in co-operation with Yoichi Shinkai from Kyoto University, Japan, and Xiaodong Cheng at Emory University, U.S.A., has now discovered new non-histone targets for an epigenetic modification enzyme previously believed to only modify histones. The research is reported current online issue of Nature Chemical Biology (doi 10.1038/nchembio.88).

[ Apr 28, 2008]  Enzymes regulating genetic expression can be just as important as the genome itself as increasing evidence shows. The expanding field of epigenetics, which considers the genetic propagation of traits from the parent to the offspring generation by mechanisms other than DNA sequence changes, focuses on the multiple influences on DNA and surrounding molecules that determine whether genes are turned on or off during development and disease processes.

Protein methyltransferases are enzymes that modify and regulate other proteins by adding methyl groups to lysine amino acids. These enzymes are often found within the histones, a group of proteins that create tightly bundled packages of DNA strands. The methylation of lysines in histones can regulate the expression of genes. The non-histone target proteins newly identified by Jeltsch and his co-workers add yet another layer of control and intracellular signalling by protein methylation. The international research team has found that a histone methyltransferase called G9a adds methyl groups to other proteins in addition to histones and changes the behaviour of those proteins. The researchers used a peptide array technology called SPOT to systematically identify the new enzyme targets.

"This discovery has two important implications" says principal investigator Albert Jeltsch. “First, it indicates that enzymes previously thought only to act on very specific histone targets, might actually have a much broader target range and therefore play a much larger role in gene regulation. Second, it reminds us that molecular biological processes, we have attributed certain functions to, actually might be much more complex than expected. In this case protein methylation might not only be used for the regulation of gene expression, but might also be part of signalling systems to regulate other intracellular processes.”