Trimethyl marks prove reversible

A family of enzymes that specifically reverses a type of histone methylation long thought to be permanent has finally come to light. The methylation state of lysine and arginine side chains on DNA-packaging histone proteins helps to control access to and transcription of genomic DNA. Such methylation is regulated by histone methylase and demethylase enzymes. Enzymes that can strip methyl groups from both di- and monomethylated side chains have been identified, but it has remained unclear whether enzymes capable of demethylating histones bearing trimethyllysine (shown) exist. Confirming that the trimethyl mark is indeed reversible, a team led by Yang Shi of Harvard Medical School has now pinpointed such enzymes (Cell 2006, 125, 467). JMJD2A and its relatives use Fe(II) and a-ketoglutarate as cofactors to carry out hydroxylation-mediated demethylation, Shi's team reports. JMJD2A removes just one methyl group from trimethyllysine, while other relatives remove two.