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Abstract Histone post-translational modifications (PTMs) participate in the dynamic regulation of chromatin structure and function, through their chemical nature and specific location within the histone sequence. Alternative analytical approaches for histone PTM studies are required to facilitate the differentiation between ubiquitously present isomers and the detection of low-abundance PTMs Here, we report a high-sensitivity bottom-up method based on nano-liquid chromatography (nLC), trapped ion mobility spectrometry (TIMS), data-dependent acquisition (DDA), parallel accumulation-serial fragmentation (PASEF), and high-resolution time-of-flight tandem mass spectrometry (ToF-MS/MS) for the analysis of histone PTMs. This method was tested in a threatened coral species, the staghorn coral Acropora cervicornis, during an episode of acute thermal stress. The obtained results allowed for the identification of PTM changes in core histones involved in the coral’s heat response. Compared to traditional LC-MS/MS approaches, the incorporation of TIMS and ddaPASEF MS/MS resulted in a highly specific and sensitive method with a wide dynamic range (6 orders of magnitude). This depth of analysis allows for the simultaneous measurement of low-abundance PTM signatures relative to the unmodified form. An added advantage is the ability to mass- and mobility-isolate prior to peptide sequencing, resulting in higher confidence identification of epigenetic markers associated with heat stress in corals (e.g. increased H4 4–17 with 2ac and 3ac, and decreases in H4 4–17 K12ac, K16ac, H4 K20me2, and H2A K5ac, K7ac, K9ac, K12ac, K14ac, and K74ac). 

Abstract Coral bleaching is the largest global threat to coral reef ecosystem persistence this century. Advancing our understanding of coral bleaching and developing solutions to protect corals and the reefs they support are critical. In the present article, we, the US National Science Foundation–funded Coral Bleaching Research Coordination Network, outline future directions for coral bleaching research. Specifically, we address the need for embedded inclusiveness, codevelopment, and capacity building as a foundation for excellence in coral bleaching research and the critical role of coral-bleaching science in shaping policy. We outline a path for research innovation and technology and propose the formation of an international coral bleaching consortium that, in coordination with existing multinational organizations, could be a hub for planning, coordinating, and integrating global-scale coral bleaching research, innovation, and mitigation strategies. This proposed strategy for future coral bleaching research could facilitate a step-function change in how we address the coral bleaching crisis.