Histone H3.5 (H3.5)

Histone H3.5 is a human-specific, non-allelic variant of histone H3, encoded by the H3-5 (H3F3C) gene, and is evolutionarily derived from H3.3[2][4]. It functions as a core component of nucleosomes, which organize genomic DNA into chromatin and regulate its accessibility for transcription, replication, and repair[4]. H3.5 is distinguished by several amino acid substitutions compared to canonical H3.3, notably Leu103, which renders nucleosomes containing H3.5 less stable than those with H3.3[2]. This instability is believed to contribute to dynamic chromatin regions, particularly around transcription start sites (TSSs) in the testis, where H3.5 accumulates and may modulate gene expression during spermatogenesis[2]. Unlike most histone genes, H3-5 is polyadenylated and contains introns[4]. H3.5 colocalizes with euchromatin and is preferably associated with active genes[4]. Although there are associations with glioma, no direct drug interactions, biomarker uses, or defined therapeutic targeting roles are established for H3.5[4]. Its primary relevance is in chromatin biology and testis-specific gene regulation.

Other names

Histone H3.3CH3-5H3F3CH3.3CH3 histone family member 3Chistone H3.5histone variant H3.5