What is Histone Protein?
Generally, in biology, histones refer to the proteins of superior quality which is most abundantly found in lysine and arginine residues, which is abundantly present in eukaryotic cell nuclei.
Histones generally acts as a spool around DNA, which winds to create the structural units commonly known as nucleosomes. Nucleosomes are wrapped into a fibre of length 30 nanometre which forms a tight wrap around the chromatin.
Histones also prevent the DNA from becoming tangled or damaged. In addition to this histone also plays an important role in regulation of gene and in DNA replication.
Without the histones, unwinding of DNA in the chromosomes take a great time. For Instance, human cell contains about 1.8 meters of DNA, if it is stretched out completely.
When it is wounded with histones its size is reduced to about 90micrometers which is of 30nm in diameter of chromatin fibres.
Generally, histones are classified into five families, which are designates as H1, H2, H3, H4 and H5. These core formation of nucleosome has two H2A-H2B dimers and a tetramer as H3-H4.
During the tight wrapping of DNA with histones its extents to a large degree of electrostatic attraction between the positively charged lysine which thereby weakens the electrostatic attraction between the positively charged histones and a negatively charged phosphate which forms the backbone of DNA.
Chemical Nature of Histones
Histones are chemically modified with the help of enzymes which regulates the transcription in the genes. The most usual modifications are methylation of arginine or lysine residues or sometimes the acetylation of lysine.
Methylation effects the proteins of transcriptions factors which interact with the nucleosomes.
Acetylation of lysine weakens the electrostatic attraction between the histone and the DNA; which results in unwinding of DNA and makes it more accessible for the expression of genes.
Classes and Variants of Histones
As mentioned earlier histones are composed of five major families ranging from H1 TO H5. Where as the histones H2, H3, H4 are known as core proteins and the histones H1 and H5 are known as linker histones.
The core histones exist as dimers that are similar to that histone fold domain. Two alpha helixes are linked by two loops, which is the helical structure that allows the interaction between distinct dimers especially in between head and tail regions.
Then the resultant four dimers come together to form one octameric nucleosome core, which weighs approximately of Angstroms.
The linker H1 binds the nucleosome at the entry till the end sites in the DNA, which helps in locking the DNA in its place and allows the formation of higher order structure.
The most basic such formation results in the formation of string conformation with beads which is of 10nm as a fibre, which helps in wrapping of chromosome around the nucleosomes with an approximate of 50 pairs which separates the pair of nucleosomes.
Structure of Histones
The nucleosome core is made up of two dimers namely H2A-H2B and H3-H4which are nearly symmetrical halves by a tertiary structure.
The H2A-H2B dimers and H3-H4 tetramer also show the pseudodyad symmetry. Whereas the four-core histone are relatively similar in structure and they are highly conserved through elevation, which features a helix to turn into helix motif.
They also have a feature of long tails at one end which carries an amino acid structure of being the location of post-translational modification.
Archael histones contains H3-H4 like dimeric structure which stacks it into a tall superhelix onto which DNA coils similar to that of nucleosome spools.
Only few archael histones have tail. The distance between the spools in the eukaryotic cells ranges from 59 to 79 angstrom which winds the DNA.
Histones and their Interactions with DNA
All histones have the capability to make five types of interactions with histones. They are as follows, Salt bridges and hydrogen bonds between the chains of amino acids and phosphates of oxygen in DNA.
Helix-dipoles forms alpha-helixes in h2b, h3 and h4 which causes a net positive charge to accumulate at the point of interaction with the negatively charged groups of phosphate on DNA.
Hydrogen bonds between the backbone of DNA and the amide group in the main chain of histone proteins. Nonpolar interactions between the histone and deoxyribose in the DNA.
Non-specific minor grooves intersect into the two minor groove on the DNA molecule. Generally, genes are active and are less bound to histone, where inactive genes are highly associated with histones during the period of interphase.
It is also confirmed that structure of histones is evolutionarily conserved though the deletion mutations are severely maladaptive.
All histones are highly positively charged with lysine’s and arginine residues.
Function of Histone
Histones generally acts as a spool which winds around the DNA. Thus, enabling to fit the large genomes of eukaryotes inside the nucleus of the cell. Where the compact molecule is 40,000 timed shorter than the unpacked molecule.
Regulation of Histones
Histones undergoes pot translational modifications which alters the interaction between DNA and the nuclear proteins.
The H3 and H4 histones contains longer tails which protrudes out of the nucleosome, which is modified covalently at several places.
Modifications takes place through methylation, acetylation, phosphorylation, ubiquitination, SUMOylation, citrullination and ribosylation with ADP.
The core of histones can also be modified. Combinations of modifications constitutes a code which is known as histone code.
These modifications act in diverse biological processes like gene regulation, DNA repair, condensation of chromosome and in spermatogenesis.
- Overview of Histone Modification. Adv Exp Med Biol . 2021;1283:1-16.
- Histones and genome integrity. Front Biosci (Landmark Ed) . 2012 Jan 1;17:984-95.
- Linker histones: History and current perspectives. Biochim Biophys Acta . 2016 Mar;1859(3):431-5.
- The language of covalent histone modifications. Nature . 2000 Jan 6;403(6765):41-5.