Utilizing intein trans-splicing for in vivo generation of site-specifically modified proteins

Abstract Many cellular processes as well as their associated pathologies are regulated by protein post-translational modifications (PTMs). Understanding the precise roles of these adducts hinges on the development of methods to robustly and site-specifically manipulate proteins in their physiological environments. Recently, ultrafast intein protein trans-splicing (PTS) was harnessed to incorporate site-specific modifications on cellular chromatin in live cells. In this chapter, we present the protocols for the generation of synthetic modifications on native chromatin as well as highlight the capabilities of this methodology.