ABSTRACT
Histones constitute the chief protein component of DNA. They help to maintain chromatin structure and regulate gene expression. The long double-stranded DNA molecule winds around histone octamers to form nucleosomes which serve the purpose of compacting DNA within the confines of the nuclear membrane. There are five major types of histones, namely H1/H5, H2, H3 and H4. H3.3 is a subtype of H3 histone and can be encoded either by the H3F3A or H3F3B genes independently. Amino acids such as lysine and arginine found in the histone tails are sites of post-translational modifications (PTMs) such as methylation and acetylation. These PTMs in histones are involved in the regulation of gene expression by chromatin remodelling and by controlling DNA methylation patterns. Mutations in histone genes can affect sites of PTMs causing changes in local and global DNA methylation status. These effects are directly linked to neoplastic transformation by altered gene expression. Recurrent H3.3 histone mutations are increasingly identified in several malignancies and developmental disorders. The following review attempts to shed light on the diseases associated with H3.3 histone mutations.
