Histones and Histone Variants

Histones are highly conserved basic proteins which associate with DNA with a definite stoichiometry to constitute the 'nucleosome' that are essential for the packaging of the genomic DNA into compact structures. There are 5 types of histones namely H2A, H2B, H3, H4 and H1 linker histone. Within a nucleosome, they exist as two dimers of (H2A-H2B) and a complex of (H32-H42) ultimately forming an octamer. H1 linker histone associates externally with the nucleosome and helps in further compaction of the chromatin structure.

Histone proteins have a characteristic 'histone fold domain' which consists of structural motif called ‘helix-turn-helix' that consists of 3 alpha helices connected by loops. Each histone perfectly fits with the counterpart to form a heterodimer that structurally gives an appearance of a hand-shake. Histones are buried inside the core structure of the nucleosome. N-terminal tails of all histones are particularly of interest since they protrude out of the compact structure. These N-terminal tails are often subjected to a variety of post-translational modifications such acetylation, methylation, phosphorylation, ubiquitination etc. The combinations of these marks on histones determine which factors bind to that region of DNA and eventually regulate the expression status of the particular locus. Histone genes are typically transcribed from multiple loci which occur as distinct clusters on different chromosomes.

Each type of histone protein has its own repertoire of variants that differ in their amino acid sequence mostly in the N-terminal region. We found a total of 55 unique histone variants present in humans. Depending on the type, the expression of a variant can be replication-dependent or replication-independent. Major function of these variants is to mark a specific region of the DNA by replacing canonical histone from the nucleosomes present at that site. This highlighting of special regions in the genome has a significant role in recruitment of different factors to that site resulting in differential treatment. This mechanism lays the foundation for the creation of an epigenetic 'memory'.

Types of histones Histone H1, Histone H2A, Histone H2B, Histone H3, Histone H4