Genetic Incorporation of ε-N-2-Hydroxyisobutyryl-lysine into Recombinant Histones

Here, we report the evolution of an orthogonal amber suppressor pyrrolysyl-tRNA synthetase (PylRS)/tRNA(CUA)(Pyl) pair that genetically encodes the post-translationally modified amino acid, epsilon-N-2-hydroxyisobutyryl-lysine (HibK), in bacteria and mammalian cells. HibK is a new type of histone mark that is widely distributed in histone proteins. The ability to site-specifically incorporate HibK into proteins provides a useful tool to probe the biological function of this newly identified post-translational modification.