Genetically directing epsilon-N, N-dimethyl-L-lysine in recombinant histones

A molecular understanding of the biological phenomena orchestrated by lysine NE-methylation is impeded by the challenge of producing site-specifically and quantitatively methylated histones Here, we report a general method that combines genetic code expansion and chemoselective reactions, for the quantitative, site-specific installation of dimethyllysine in recombinant histones We demonstrate the utility of our method by preparing H3K9me2 and show that this modified histone is specifically recognized by heterochromatin protein 1 beta Extensions of the strategy reported here will allow a range of chemoselective reactions (which have been used for residue-selective, but not site-selective protein modification) to be leveraged for site-specific protein modification