Glutamate Methylation, a Novel Histone Mark in Diatoms: Mass Spectrometry Identification and Structural Characterization.

Abstract

Post-translational modifications of histones (PTMs) play a crucial role in regulating chromatin function. These modifications are integral to numerous biological processes, including transcription, DNA repair, replication, and chromatin remodeling. Although several PTMs have been identified, enhancing our understanding of their roles in these processes, there is still much to discover given the potential for virtually any histone residue to be modified. In this study, we report the discovery of a novel PTM in the model diatom Phaeodactylum tricornutum, glutamate methylation identified by mass spectrometry at multiple positions on histone H4 and at position 96 on histone H2B. This modification was also detected in other model organisms, including Drosophila melanogaster, Caenorhabditis elegans, and humans, but not in Arabidopsis. Structural bioinformatics analyses, including molecular dynamics simulations, revealed that methylation of glutamate residues on histones induces displacement of these residues, exposing them to solvent and disrupting interactions with neighboring residues in associated histones. This disruption may interfere with histone complexes promoting histone eviction or facilitating interactions with regulatory proteins or complexes, which may compromise the overall nucleosome stability.