Chemical tools for trapping histone modification enzymes on nucleosome substrates for structural studies

Histone post-translational modifications (PTMs) serve as gatekeepers for our genome through regulation of protein recruitment and modulation of chromatin structure. Dysregulation of the enzymes that add and remove histone PTMs is common in diverse disease states and histone modifying enzymes are emerging as important therapeutic targets. As such, it has been a priority to understand molecular mechanisms governing histone modifying enzyme function on physiologic nucleosome substrates. However, structural studies remain challenging due to the inherent low affinity and transient nature of many enzyme-nucleosome interactions. Over the last decade a growing number of chemical biology tools have been reported to trap histone modifying enzymes in action on nucleosomes for structural biology. We took this opportunity to review these strategies and highlight recent advances they have enabled in chromatin biology.