Proteomic characterization of novel histone post-translational modifications

Abstract

Histone post-translational modifications (PTMs) have been linked to a variety of biological processes and disease states, thus making their characterization a critical field of study. In the last 5 years, a number of novel sites and types of modifications have been discovered, greatly expanding the histone code. Mass spectrometric methods are essential for finding and validating histone PTMs. Additionally, novel proteomic, genomic and chemical biology tools have been developed to probe PTM function. In this snapshot review, proteomic tools for PTM identification and characterization will be discussed and an overview of PTMs found in the last 5 years will be provided.

Figure 1

Recently identified modifications on the core histones. Black, modifications found in vivo in human; red, modifications found in mouse brain; blue, modifications found in vitro. ac, acetylation; Ar, ADP-ribosylation; bu, butyrylation; cr, crotonylation; fo, formylation; gt, glutathionylation; ma, malonylation; me, methylation; Og, O-glcNAcylation; oh, hydroxylation; pr, propionylation; su, succinylation; ph, phosphonylation; ub, ubiquitination.

Figure 2

Global domain post-translational modifications. (a) The nucleosome with H3 (blue), H4 (green), H2A (red) and H2B (yellow). (b) Tryosine hydroxylation on H2BY83 (cyan) and H4Y88 (purple) occur at the H2B:H4 interface. (c) Glutathionylation of H3C110 mapped to the H3:H4 tetramer interface. (d) Phosphorylation on H3T45 (pink) and H3Y41 (yellow) mapped to the H3:H4 tetramer. (e) Phosphorylations from (d) occur near the H3:DNA contact.