Fig. 3

Described natural functions of histones. After being synthesized in the cytoplasm, histones undergo transportation to the nucleus, where they play a role in regulating DNA condensation and gene transcription. Alternatively, histones can serve extranuclear functions, either within the cytoplasm or in the extracellular space. Those transported from the cytoplasm may either remain bound to membranes or be released into the extracellular space, exhibiting a broad-spectrum antimicrobial activity against bacteria, viruses, parasites, and fungi. In the cytoplasm, histone H1 is associated with lipid droplets and is released upon stimulation with endotoxin or lipoteichoic acid. Additionally, histone H2B acts as a sensor for viral dsDNA. Nuclear histones ultimately contribute to neutrophil extracellular traps, playing a crucial role in neutrophil extracellular trap-mediated bacterial killing. “Created with BioRender.com”