Reading the Combinatorial Histone Language

Histones are subject to frequent combinatorial post-translational modifications (PTMs), forming a complex chemical language that is interpreted by PTM-specific histone-interacting protein modules (reader domains). These specific interactions are thought to instruct gene expression and downstream biological functions. While the majority of studies have focused on individual modifications, our current understanding of the combinatorial PTM patterns on histones is starting to emerge, benefiting from the convergence of multiple technologies. Here, we review the key technical advances and progress on discovery and characterization of combinatorial histone PTM patterns. We focus on the interactions between reader domains and combinatorial PTMs, which is essential for understanding the mechanism and biological meaning of establishing and interpreting information embedded in histone PTM patterns.