Histone H3 is a core component of the nucleosome, the fundamental unit of chromatin, which plays a crucial role in organizing genomic DNA within the eukaryotic nucleus. The citrullination of Histone H3 at arginine residues R2, R8, and R17 is a specific post-translational modification catalyzed by peptidyl arginine deiminase 4 (PAD4). This modification prevents methylation of these residues by protein-arginine methyltransferase 4 (PRMT4) and is associated with transcriptional repression. Citrullinated Histone H3 is also a key component of neutrophil extracellular traps (NETs) and acts as an autoantigen, contributing to the production of anti-citrullinated protein antibodies in various diseases, including sepsis, multiple sclerosis, rheumatoid arthritis, and multiple myeloma.
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