Histones are proteins that package DNA into nucleosomes. Histones are responsible for maintaining the shape and structure of nucleosomes. A chromatin molecule consists of at least one of every core histone in every 100 DNA base pairs. There are five families of histones known to date. Together these histones are considered core histones. The formation of the core first occurs through the interaction of two H2A molecules. Then, H2A forms a dimer with H2B. When H3-H4 also attaches to form a tetramer, the core molecule is complete.
Histone h2a protein consists of a major globular domain, an N-terminal tail, and a C-terminal tail. Both tails are positions of post-translational modifications. So far, the researchers haven't found any secondary structures that appear in the tail. H2A utilizes protein folding called "histone folding". The histone fold is a triple-helix core domain connected by two loops. This connection forms a "handshake arrangement". Most notably, this is called a helix-turn-helix motif, which allows dimerization with histone h2b protein. The "histone fold" is conserved in H2A at the structural level, however, the gene sequence encoding this structure differs between variants.
The structure of the macro h2A variant was revealed by X-ray crystallography. Conserved domains contain DNA-binding structures and peptidase folds. The function of this conserved domain remains unknown. Studies have shown that this conserved domain may act as an anchoring site for DNA, as well as as a modifying enzyme.
DNA folding: H2A is important for packaging DNA into chromatin. Since H2A packages DNA molecules into chromatin, the packaging process affects gene expression. H2A is associated with DNA modifications and epigenetics. H2A plays a major role in determining the overall structure of chromatin. It was accidentally discovered that H2A can regulate gene expression.
Modification of DNA by H2A occurs in the nucleus. The proteins responsible for the nuclear import of histone H2A proteins are nuclear transporters and importins. Recent studies have also shown that nucleosome assembly protein 1 (NAP1) is also used to transport H2A into the nucleus so it can wrap DNA. Additional functions of histone H2A protein have been found in the histone variant H2A.Z. This variant is associated with gene activation, silencing and repression by antisense RNA. Furthermore, when H2A.Z was studied in human and yeast cells, it was used to promote the recruitment of RNA polymerase II.
In vertebrates and invertebrates, histone H2A variants have been reported to participate in host immune responses by acting as antimicrobial peptides (AMPs). H2A is an α-helical molecule, belonging to the amphiphilic protein, with hydrophobic and hydrophilic residues on opposite sides, which can enhance the antibacterial activity of H2A.