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The nucleosome core particle consists of an octamer containing four types of histone proteins: H2A, H2B, H3, and H4. Each histone type is small, containing up to 135 amino acids, and shares a common structural motif called the histone fold. Two copies of each histone protein combine to form the complete octamer that serves as the core around which DNA wraps.

Histone proteins assemble through a stepwise process. First, histone folds bind to each other in a handshake interaction, forming two H2A-H2B dimers and two H3-H4 dimers. The H3-H4 dimers then form a tetramer, which combines with the H2A-H2B dimers to create the complete histone octamer of the nucleosome core particle.

Histones are highly conserved because nucleosome core particles play an essential role in controlling DNA compaction and chromatin structure. This critical function has been preserved across eukaryotes from peas to cows. For example, H4 histones differ by only two amino acids out of 102 between pea plants and cows, demonstrating their evolutionary conservation.

More than 100 hydrogen bonds stabilize DNA binding to the histone octamer. Many of these bonds form between the amino acid backbones of histones and the sugar-phosphate backbone of DNA. Additionally, lysine and arginine amino acids in core histones carry positive charges that neutralize the negatively charged DNA backbone, further strengthening the interaction.

The histone fold is a common structural motif shared by all four core histone proteins, consisting of three alpha-helices connected by two loops. During nucleosome assembly, histone folds bind to each other in handshake interactions to form histone dimers. This conserved structure is essential for proper histone-histone interactions and subsequent DNA binding.

Histone variants like H2A.Z, H2A.X, and H3.3 differ from standard core histones in their amino acid sequences and perform distinct cellular functions. Nucleosomes containing histone variants are significantly more mobile than ordinary nucleosomes. For example, incorporation of H2A.Z into the nucleosome activates transcription, demonstrating how variants modify chromatin function.

Chemical modifications to histone tails, such as acetylation, methylation, and phosphorylation, can modify chromatin assembly and function. The alpha-helix and N-terminal tail of each histone protein play crucial roles in DNA binding, making these regions sensitive to modification. Such changes allow nucleosomes to regulate DNA access for replication and transcription while maintaining DNA protection.