REMY: A platform for the rapid interrogation of epigenome modifications on yeast

Histone proteins are decorated with a combinatorially and numerically diverse set of biochemical modifications. Here we describe a versatile and scalable platform termed Rapid interrogation of Epigenome Modifications using Yeast surface display (REMY), which enables efficient characterization of histone modifications without the need for recombinant protein production. As proof-of-concept, we first used REMY to rapidly profile the histone H3 and H4 residue writing specificities of the human histone acetyltransferase, p300. Subsequently, we used REMY to screen a large panel of commercially available anti-acetylation antibodies for their specificities, identifying many suitable and unsuitable reagents. Further, use of REMY enabled efficient mapping of the large binary crosstalk space between acetylated residues on histones H3 and H4, and uncovered previously unreported residue interdependencies affecting p300 activity. Our results show that REMY is a useful tool that can advance our understanding of chromatin biology by enabling efficient interrogation of the complexity of epigenome modifications.