Accelerating the Field of Epigenetic Histone Modification Through Mass Spectrometry–Based Approaches

Histone post-translational modifications (PTMs) are one of the main mechanisms of epigenetic regulation. Dysregulation of histone PTMs leads to many human diseases, such as cancer. Because of its high throughput, accuracy, and flexibility, mass spectrometry (MS) has emerged as a powerful tool in the epigenetic histone modification field, allowing the comprehensive and unbiased analysis of histone PTMs and chromatin-associated factors. Coupled with various techniques from molecular biology, biochemistry, chemical biology, and biophysics, MS has been used to characterize distinct aspects of histone PTMs in the epigenetic regulation of chromatin functions. In this review, we will describe advancements in the field of MS that have facilitated the analysis of histone PTMs and chromatin biology. [Display omitted] •Middle–down is the most suitable to study histone combinatorial post-translational modifications.•Crosslinking MS has a variety of potential applications in exploring histone post-translational modifications.•Hydrogen–deuterium exchange MS holds great promise to study the compaction of nucleosome.•Multi-omics approaches are useful to study complex regulatory networks. Histone post-translational modifications play essential roles in the epigenetic regulation of chromatin-related functions. Because of its high throughput, accuracy, and flexibility, mass spectrometry has emerged as a powerful tool in the epigenetic field. In this review, we describe the contributions of mass spectrometry–based proteomics in combination with distinct labeling strategies and various biological techniques to understand the roles of histone post-translational modifications and how they regulate chromatin function.