Histone

Histones are highly conserved basic nuclear proteins that package and organize DNA in eukaryotic cells. The core histones—H2A, H2B, H3, and H4—assemble into an octamer consisting of a (H3-H4)2 tetramer flanked by two H2A–H2B dimers. About 146 base pairs of DNA wrap around this octamer to form the nucleosome core particle, while the linker histone H1 binds the DNA between nucleosomes to promote higher-order chromatin structure.

Nucleosomes are the fundamental units of chromatin. Histone proteins possess N-terminal tails that extend from the core particle and are targets for post-translational modifications, including acetylation, methylation, phosphorylation, ubiquitination, and sumoylation. Collectively these marks contribute to the histone code, influencing chromatin compaction, nucleosome stability, and recruitment of chromatin-modifying enzymes and transcription factors to regulate gene expression.

Histone variants and chaperones add functional diversity. Variants such as H2A.Z, H3.3, CenH3 (CENP-A), macroH2A, and H2A.X replace standard histones in specific contexts to alter nucleosome properties or signaling. Histone chaperones (e.g., CAF-1, ASF1, HIRA) assist with histone deposition and exchange during DNA replication, repair, and transcription. Replication-coupled histones (H3.1, H4) are incorporated during S phase, while replication-independent variants (e.g., H3.3) can be deposited throughout the cell cycle.

Histones play central roles in DNA packaging, replication, repair, and transcription, with chromatin-modifying enzymes and remodelers modulating their post-translational state to regulate genome function.