Obesity Gene Encodes Demethylating Enzyme

Earlier this year, British scientists reported that a gene called FTO is associated with obesity. But the protein encoded by FTO remained unknown. Now, a second British team, led by chemist Christopher J. Schofield of the University of Oxford, reports that the FTO gene encodes an enzyme that removes methyl groups from nucleic acids (Science, DOI: 10.1126/science.1151710). The enzyme requires both iron(II) and 2-oxoglutarate to be active. In vitro, the enzyme catalyzes demethylation of 3-methylthymine, forming succinate, formaldehyde, and carbon dioxide in the process. The enzyme's closest relatives are members of the AlkB family of enzymes, which repair damaged DNA. Schofield and coworkers still don't know the enzyme's natural substrate or the role demethylation may play in obesity. Andrew Hattersley, professor of molecular medicine at Peninsula Medical School, in Exeter, England, and a member of the team that found the FTO-obesity connection, calls the new work an "important step in understanding the biology" of the FTO gene.