{"type": "root", "children": [{"type": "p", "children": [{"type": "t", "text": "\n Recent work has revealed that post‐translational modifications on histone H4 play a central role in regulating chromatin structure and function. In these studies, acetylation of H4—most notably at lysine 16—has been shown to relax nucleosomal arrays, thereby inhibiting compaction and facilitating access of chromatin‐remodeling and DNA repair factors, while deacetylation is critical for assembling condensed, mitotic chromatin and centromeric chromatin formation."}, {"type": "fg", "children": [{"type": "fg_fs", "start_ref": "1", "end_ref": "3"}]}, {"type": "t", "text": " In parallel, methylation marks on H4—such as dimethylation of lysine 20—serve as recognition sites for specific effector modules (for example, tandem Tudor domains), which are essential for targeting proteins involved in the DNA damage response and repair."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "4"}]}, {"type": "t", "text": " Such modifications further influence centromere identity and proper nucleosome assembly by contributing to the recruitment of specialized histone variants."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "5"}]}, {"type": "t", "text": " Moreover, histone H4 marks are dynamically regulated by enzymes whose activities are coupled to cellular metabolic states and stress signals; for instance, shifts in H4 acetylation mediate the interplay between nutrient status and transcription, impacting processes as diverse as neurogenesis, muscle stem cell activation, and long‐term memory formation."}, {"type": "fg", "children": [{"type": "fg_fs", "start_ref": "6", "end_ref": "8"}]}, {"type": "t", "text": " Collectively, these findings underscore the multifaceted functions of H4 “C6” (that is, the H4 molecule and its complex modification repertoire) in coordinating chromatin dynamics, ensuring genomic integrity, and integrating environmental and intracellular signals to modulate gene expression.\n "}]}, {"type": "rg", "children": [{"type": "r", "ref": 1, "children": [{"type": "t", "text": "Michael Shogren-Knaak, Haruhiko Ishii, Jian-Min Sun, et al. 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