Abstract:Histone post-translational modifications are key epigenetic mechanisms, which modulate gene expression without altering the DNA sequence. The acylation of histones, particularly the well-known histone acetylation, is a crucial type of histone post-translational modification. Recent advancements in high-sensitivity mass spectrometry have facilitated the identification of various metabolic intermediates and end products that modify histones, leading to the discovery of novel acylation modifications. These novel histone acylations significantly influence nucleosome stability and chromatin accessibility, thereby playing an important role in the epigenetic regulation of physiological and pathological processes. Exposure to external stressors induces alterations in cellular metabolism, and the metabolites subsequently modulate gene expression via histone acylation. This pathway represents a crucial mechanism by which environmental factors shape the phenotypes of organisms. This paper provides a comprehensive review of 16 novel histone acylation modifications, detailing their writers, readers, and erasers, and elucidating their role in the epigenetic regulation of aging, development, tumor progression, and metabolism. Furthermore, it summarizes the relationship between novel histone acylation modifications and organismal metabolism, discusses the technical challenges encounter in the study of these modifications, and explores the future research directions of novel histone acylation modifications as well as their potential clinical applications.
