- 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 6 nm 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 the nucleosome is invariable in all the eukaryotes.
- P. Oudet et al. (1975) worked extensively on the structure of nucleosomes and proposed that the length of the 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 the ‘Solenoid model of nucleosome’.
- This model describes the dense compaction of DNA in chromosomal chromatids.
- It further illustrates that chromatin fibers tightly coil in a chromosome and form lump-like structures.
- 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 a DNA segment of 200 base pairs was found forming one3/4 turn.
- Through the process of supercoiling, such nucleosomes with the help of linker DNA easily form the solenoid-like structure.
- It was also shown that an 11 nm wide fiber of nucleosomes gets coiled upon itself to form – 30 nm wide helix with five or six nucleosomes per helix.
- In this helix successive nucleosome units came close together, so that their center to center distance was about 10 nm.
- This 30 nm 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 fiber into 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 solenoids.
- 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 30 nm wide solenoid fibers, giving 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, which 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 nucleosomes 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.