Histones

histone

Histones

Histones are a group of proteins that associate with DNA in the nucleus and help to condense it into chromatin. They are alkaline protein and their positive charge allow them to associate with DNA. They are found inside the nucleus of eukaryotic cell.

Nucleosome consists of DNA wrapped around 8 histone protein called histone octamer. DNA and histone are packed together to be nucleosome, nucleosome form a pack which are called chromatin, 2 chromatin forms a chromosomes.

Types of Histone:-

Histone protein are of 2 types

  1. Core histone
  2. Linker histone

Core histone- H2A, H2B, H3 & H4

Linker histone- H1 & H5

Each histone protein assemble to form 1 octameric nucleosome core particle and 147 base of DNA wrap around this core particle.

histone octamer

H2A is important for packaging DNA into chromatin. Since H2A package  DNA molecules into chromatin, the packaging process will effect gene expression. H2A  has been correlated with DNA modification. H2A plays a major role in determining the overall structure of chromatin. H2A has been found to regulate gene expression.

H2B is also involved with structure of the nucleosomes of the beads on a string structure.

H3 is involved in the structure of chromatin in eukaryotic cells. Featuring a main globular domin and a long N-terminal tail.H3 is an important protein in the emerging feild of epigenetics, where its sequence varients and variables modification atates are thought to play a role in the dynamic and long term regulation of gene.

H4 is involved in the structure of chromatin in eukaryotic cell. H4 is a structural component of the nucleosome and is subject to covalent modification including acetylation and methylation, which may alter expression of genes located on DNA associated with its parent histone octamers.

H1 is one of the 5 main histone protein families which are components of chromatin in eukaryotic cells. H1 does not make up the nucleosomes beads. It sits on the top of the structure, keeping in place the DNA that has wrapped around the nucleosomes. It is present in half of the other 4 histone, which contribute 2 molecules to each nucleosomes bead.

H5 histones are individual protein involve in the packing of specific regin of DNA.

Packaging of Histones
In the core of nucleosomes the 2 dimer H2A and H2B and tetramer H3 and H4 are involve and form the tertiary structure. Histone are highly positively charge and have lysine and arginine residues.

Histone modification
All the histone protein are chemically modified. Chemically modification of histones are associated with structural change that occurs at the time of replication and transcription. The 3 most common types of chemical modification are:

  • Acetylation
  • Methylation
  • Phosphorylation

Histone acetylation and deacetylation

Acetylation:- All the core histone are acetylated. The major target for acetylation are lysine 1 the N-terminals tails of histones H3 & H4. Acetylation occurs in 2 different circumstances:-

Acetylation occurs before the histones are incorporated into nucleosomes.Acetyl group are added to the lysine amino acids in the histone tail each of the core molecules. Acetylation is reversible. Enzymes that acetylated histones are acetyl transferases (HATs),  commonly known as histone acetylases. 2 group of HATs enzyme those are:

  • Group A act on histone in chromatin and involved with control of transcription.
  • Group B act on newly synthesized histone in cytosol and are involved with nucleosomes assembly.

Acetylation reduces the affinity of the histones for DNA and possibly aldo reduces the interaction between the individual nucleosomes that leads to formation of chromatin fibre.

Enzyme histone Deacetylases (HDACs) catalyze the removal of acetyl group (i.e deacetylation). The in heterochromatin are generally deacetylated whereas those in euchromatin are acetylated.

acetylation and deacetylation

The important effect on nucleosome structure:

  • At replication, acetylation of histone could be necessary to allow them to be incorporated into new cores more easily.
  • At transcription, a similar effects could be necessary to allow a related change in structure, possible even to allow the histone core to be displaced from DNA.

Methylation:- Many lysine and arginine amino acids at the N-terminus of histone undergo methylation. Methylation at lysine or arginine may be one of the three forms; mono, di, for arginines. It is catalyzed by methyl transferases. Methylation of different part of the N-terminal of H3 and H4 histones is associated with both repressed and active chromatin, depending on the particular amino acid that is modified in the histone tail.

For example:- methylation of lysine at 9th position of H3 is associated with gene silincing/ chromatin condensation whereas methylation of lysine at 4th position of H3 is associated with transcription activation. Methylation of histones provides a site for the binding of other proteins which then leads to alteration of chromatin structure.

Protein that bind to methylated histones contain a domain called chromo domain. Histone lysine methylation plays a fundamental role in heterochromatin formation, chromosome X-inactivation, genomic imprinting and transcriptional regulation.

Phosphorylation:- Histone are phosphorylated in 2 circumstances, cyclically during the cell cycle, In association with chromatin remodeling. It has been known that histone H1 is phosphorylated at mitosis and more recently it was discovered that H1 is an extremly good substrate for the Cdc2 kinase that controls cell division. Less of a kinase that phosphorylated histone H3 on 10 Ser has devastating chromatin structure.

The cause of disruption structure is most likely the failure to phosphorylated histone H3. This suggests that H3 phosphorylation is required to generate the more extended chromosomes structure of euchromatic regions. It is important in the cell cycle, it is likely too be a single for condensation. 

Its effect in chromatin remodeling appears to be the opposite. It is of course possible that phosphorylation of different histones, or even of different amino acids add residues in one histone, has opposite effects on chromatin structure.

Histones

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