Histone tails: ideal motifs for probing epigenetics through chemical biology approaches.

Post-translational modifications (PTMs) on histone proteins have emerged as a central theme in the regulation of gene expression and other chromatin-associated processes. The discovery that certain protein domains can recognize acetylated and methylated lysine residues of histones has spurred efforts to uncover and characterize histone PTM-binding proteins. In this task, chromatin biology has strongly benefited from synthetic approaches stemming from chemical biology. Peptide-based techniques have been instrumental in identifying histone mark-binding proteins and analyzing their binding specificities. To explore how histone PTMs carry out their function in the context of chromatin, reconstituted systems based on recombinant histones carrying defined modifications are increasingly being used. They constitute promising tools to analyze mechanistic aspects of histone PTMs, including their role in transcription and their transmission in replication. In this review, we present strategies that have been used successfully to investigate the role of histone modifications, concepts that have emerged from their application, and their potential to contribute to current developments in the field.