NUCLEOSOME ORGANIZATION

NUCLEOSOME ORGANIZATION

This model was proposed by Kornberg and Thomas in 1974 to explain the structure of chromatin fibres. This has been widely accepted all over the world. According to this model, chromatin is composed of a repeating unit called nucleosome.

Important points of this model are as follows:

Chromatin fibres of a chromosome are made up of DNA and histone proteins.

The repeating unit of chromatin is called nucleosome. It is a disc like structure 11nm in diameter and 6nm in height. The core of a nucleosome is made up of an octamer of proteins having two molecules each of H2A, H2B, H3 and H4 histones.

Around this octamer, a DNA segment having the length of 200 base pairs is wound round making one 3/4 turns. This segment of DNA in chromatin fibre is nuclease resistant. The structure of nucleosome is invariable in all the eukaryotes.

P. Oudet et al. (1975) worked extensively on the structure of nucleosome and proposed that the length of DNA segment in the core of nucleosome is 146 base pairs. Two nucleosome units are joined with a segment of DNA, which is called linker. It consists of 50-70 base pairs. H1 histone is associated with this linker DNA which makes a connection between two adjacent nucleosomes.

The nucleosome, model explains the ‘string of beads’ concept of chromatin. This is just opposite, to the concept of ‘beads on string’ explaining the interrelationship of genes and chromosomes. Aron Clug (1977-80) made further electron microscopic studies of chromosomes and chromatin and proposed ‘Solenoid model of nucleosome’. This model describes the dense compaction of DNA in chromosomal chromatids. It further illustrates that chromatin fibres tightly coil in a chromosome and form lump like structure. The average diameter of this chromatin lump is 300 Å in which several nucleosomes of 100 Å diameter are found. As has been mentioned earlier each nucleosome is made up of protein octamer around which DNA segment of 200 base pairs was found forming one3/4 turn. Through the process of super coiling, such nucleosomes with the help of linker DNA easily form the solenoid like structure.

SOLENOID MODEL:

It was also shown that 11nm wide fibre of nucleosomes gets coiled upon itself to form – 30nm wide helix with five or six nucleosomes per helix. In this helix successive nucleosome units came close together, so that their centre to centre distance was about 10 nm. This 30nm structure was called a solenoid. Formation of solenoid from nucleosomes can be compared with winding of a cable on a spool and then folding of wrapped spools.

It was also proved that H1 protein helped in folding of 110 A wide fibre in to 300 armstrong wide solenoid, It has been shown that H1 molecules aggregate by cross linking to form polymers and may thus control the formation of solenoid. The above account gives patterns of coiling and packing of DNA. Since 60 nm along DNA is coiled in a nucleosome, only 6nm long, and then nucleosomes are coiled in 30nm wide solenoid fibres, it gives DNA a packing ratio of 1:50. However, in highly condensed chromosomes, the packing ratio is actually 1:5000, which is 100 times greater than provided by solenoid, would take place by further coiling and folding of solenoid.

Ubiquitination, acetylation, methylation and phosphorylation of histones in the nucleosome.

The histone proteins, which are integral parts of nucleosome undergo a variety of modifications to bring about decondensation of chromatin, to allow access of DNA replication or transcription machinery to naked DNA. These modifications include ubiquitination, acetylation, methylation and phosphorylation of some specific amino acid residues of histones.

Acetylation and methylation occur on the free amino groups of lysines residues. Methylation also occurs on arginine and histidine. Similarly, phosphorylation occurs on the hydroxyl group of serine and histidine. Methylation and acetylation remove the positive charge on NH₃⁺, while phosphorylation introduces a negative charge in the form of  phosphate group.