Téletchéa Stéphane, Lombard Bérangère, Hendrickx Johann, Loew Damarys, Tirichine Leïla
Nantes Université, CNRS, US2B, UMR 6286 Nantes France.
Institut Curie PSL Research University, Centre de Recherche, CurieCoreTech Mass Spectrometry Proteomics Paris France.
Plant Direct. 2025 May 13;9(5):e70051. doi: 10.1002/pld3.70051. eCollection 2025 May.
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 , 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 , , and humans, but not in . 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.
组蛋白的翻译后修饰（PTMs）在调节染色质功能中起着关键作用。这些修饰是众多生物过程所不可或缺的，包括转录、DNA修复、复制和染色质重塑。尽管已经鉴定出了几种PTM，增进了我们对它们在这些过程中作用的理解，但鉴于几乎任何组蛋白残基都有被修饰的可能性，仍有许多有待发现。在本研究中，我们报告了在模式硅藻中发现的一种新型PTM，即通过质谱法在组蛋白H4的多个位置以及组蛋白H2B的96位鉴定出的谷氨酸甲基化。在包括 、 和人类在内的其他模式生物中也检测到了这种修饰，但在 中未检测到。包括分子动力学模拟在内的结构生物信息学分析表明，组蛋白上谷氨酸残基的甲基化会导致这些残基发生位移，使其暴露于溶剂中，并破坏与相关组蛋白中相邻残基的相互作用。这种破坏可能会干扰促进组蛋白驱逐或促进与调节蛋白或复合物相互作用的组蛋白复合物，这可能会损害整体核小体稳定性。
