Methylation Mimic Silences DNA Targets

Nature turns off transcription of a gene by adding a methyl group to the gene. A new silencing technique puts that same ability in the hands of scientists. Cells rely on methyltransferases to recognize a specific DNA sequence and then attach a methyl group to one of its bases. Carlos F. Barbas III and Wataru Nomura of Scripps Research Institute have designed a self-assembling, semisynthetic methyltransferase to mimic this behavior at a specific DNA site in bacteria (J. Am. Chem. Soc., DOI: 10.1021/ja0705588). In their system, DNA binding of artificial zinc finger proteins (shown, green) brings together two fragments (orange) of methyltransferase, which then assemble into the active enzyme. The enzyme subsequently transfers a methyl group to a cytosine in the region between the two DNA binding sites. Different zinc finger proteins could be prepared to bind other DNA sequences, potentially making the technique broadly applicable for therapeutic gene silencing.