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Medical Definition of histone. : any of various simple water-soluble proteins that are rich in the basic amino acids lysine and arginine and are complexed with DNA in the nucleosomes of eukaryotic chromatin.
Four of the histones, H2A, H2B, H3 and H4, are involved in forming the nucleosome structure with DNA, and are referred to as core histones. Histone H3 and H4 are also involved in histone acetylation.