Histone H2A

Histone H2A is one of the five main histone proteins involved in the structure of chromatin in eukaryotic cells. Histone H2A is one of the five main histone proteins involved in the structure of chromatin in eukaryotic cells. Histones are proteins that package DNA into nucleosomes. Histones are responsible for maintaining the shape and structure of a nucleosome. One chromatin molecule is composed of at least one of each core histones per 100 base pairs of DNA.There are five families of histones known to date; these histones are termed H1/H5, H2A, H2B, H3, and H4. H2A is considered a core histone, along with H2B, H3 and H4. Core formation first occurs through the interaction of two H2A molecules. Then, H2A forms a dimer with H2B; the core molecule is complete when H3-H4 also attaches to form a tetramer. Other histone proteins:H1H2BH3H4 Histone H2A is composed of non-allelic variants. The term 'Histone H2A' is intentionally non-specific and refers to a variety of closely related proteins that vary often by only a few amino acids. Notable variants include H2A.1, H2A.2, H2A.X, and H2A.Z. H2A variants can be explored using 'HistoneDB with Variants' database Changes in variant composition occur in differentiating cells. This was observed in differentiating neurons during synthesis and turnover; changes in variant composition were seen among the H2A.1 histone. The only variant that remained constant in the neural differentiation was variant H2AZ. H2AZ is a variant that exchanges with conventional H2A core protein; this variant is important for gene silencing. Physically, there are small changes on the surface area of the nucleosome that make the histone differ from H2A. Recent research suggests that H2AZ is incorporated into the nucleosome using a Swr1, a Swi2/Snf2- related adenosine triphosphatase. Another H2A variant that has been identified is H2AX. This variant has a C-terminal extension that’s utilized for DNA repair. The method of repair this variant employs is non-homologous end joining. Direct DNA damage can induce changes to the sequence variants. Experiments performed with ionizing radiation linked γ- phosphorylation of H2AX to DNA double-strand break. A large amount of chromatin is involved with each DNA double-strand break; a response to DNA damage is the formation of γ- H2AX. Lastly, MacroH2A variant is a variant that is similar to H2A; it is encoded by the H2AFY gene. This variant differs from H2A because of the addition of a fold domain in its C-terminal tail. MacroH2A is expressed in the inactive X chromosome in females. H2A consists of a main globular domain and a long N-terminal tail or C-terminal on one end of the molecule. The N-terminal tail or C-terminal tail is the location of post-translational modification. Thus far, researchers have not identified any secondary structures that arise in the tail. H2A utilizes a protein fold known as the ‘histone fold.’ The histone fold is a three-helix core domain that is connected by two loops. This connection forms a ‘handshake arrangement.’ Most notably, this is termed the helix-turn-helix motif, which allows for dimerization with H2B. The ‘histone fold’ is conserved among H2A at the structural level; however the genetic sequence that encodes for this structure differs between variants.