Studies of biochemical crosstalk in chromatin with semisynthetic histones.

•Chromatin is regulated by biochemical crosstalk between histone marks.•Marks are written, read, and erased by chromatin-modifying enzymes.•The heterogeneity of marks complicates functional studies.•Semisynthesis yields uniformly modified histones for mechanistic studies.•Designer nucleosomes enable studies of crosstalk between histone marks.