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)/tRNACUAPyl pair that genetically encodes the post-translationally modified amino acid, e-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.