Study published in Nature Chemical Biology shows that G9a methylates other proteins including itself.
A consortium of scientists identified nonhistone targets for an enzyme previously believed to modify only histones. These modification enzymes called protein methyltransferases add methyl groups to lysine amino acids within the histones and change their influence on gene expression.
Using a peptide array technology called SPOT, the international team found that the histone methyltransferase called G9a recognizes an Arg-Lys sequence and that G9a’s activity is inhibited by methylation of the arginine residue. This specificity profile allowed the investigators to identify other proteins that G9a adds methyl groups to changing their behavior. These nonhistone targets include CDYL1, WIZ, ACINUS, and G9a (automethylation) as well as peptides derived from CSB.
“This discovery broadens our view of methyltransferases and tells us that epigenetic regulation in cells is even more complicated than we thought,” says principal investigator, Xiaodong Cheng, Ph.D., professor of biochemistry at Emory University School of Medicine. “This is an important piece of the puzzle, and additional research will continue to help us unwind the multiple mechanisms involved in epigenetic gene regulation.”
The study was conducted by investigators at Emory University School of Medicine, Jacobs University Bremen, Kyoto University, and Advanced Life Science Institute. The research was reported online on April 27 in the journal Nature Chemical Biology.
