The chromosomes are the nuclear components of the special organization, individuality, and function that are capable of self-reproduction and play a vital role in heredity, mutation, variation and evolutionary development of the species.
Each chromosome is made up of DNA tightly coiled many times around proteins that support its structure.
The proteins that bind to the DNA to form eukaryotic chromosomes are traditionally divided into two classes: the histones and the non-histone chromosomal proteins.
The complex of both classes of protein with the nuclear DNA of eukaryotic cells is known as chromatin.
Chromatin are a highly compacted structure consisting of packaged DNA and necessary so as to fit DNA into the nucleus.
The assembly of DNA into chromatin involves a range of events, beginning with the formation of the basic unit, the nucleosome, and ultimately giving rise to a complex organization of specific domains within the nucleus.
In the first step of this process, DNA is condensed into an 11 nm fiber that represents an approximate 6-fold level of compaction. This is achieved through nucleosome assembly.
The nucleosome is the smallest structural component of chromatin and is produced through interactions between DNA and histone proteins.
Each nucleosome consists of histone octamer core, assembled from the histones H2A, H2B, H3 and H4 (or other histone variants in some cases) and a segment of DNA that wraps around the histone core. Adjacent nucleosomes are connected via “linker DNA”.
Nucleosome model is a scientific model which explains the organization of DNA and associated proteins in the chromosome.
It also further explains the exact mechanism of the folding of the DNA in the nucleus.
The model was proposed by Roger Kornberg in 1974 and is the most accepted model of chromatin organization.
It was confirmed and christened by P. Oudet et al., (1975).
Features of the Nucleosome Model of Chromosomes
In eukaryotes, DNA is tightly bound to an equal mass of histones, which serve to form a repeating array of DNA-protein particles, called nucleosomes.
If it was stretched out, the DNA double-helix in each human chromosome would span the cell nucleus thousands of time.
Histones play a crucial role in packing this very long DNA molecule in an orderly way (i.e., nucleosome) into nucleus only a few micrometers in diameter.
Thus, nucleosomes are the fundamental packing unit particles of the chromatin and give chromatin a “beads-on-a-string” appearance in electron micrographs taken after treatments that unfold higher-order packing.
Each nucleosome is a disc-shaped particle with a diameter of about 11 nm and 5.7 nm in height containing 2 copies of each 4 nucleosome histones–H2A, H2B, H3, and H4.
This histone octamer forms a protein core [(i.e., a core of histone tetramer (H3, H4)2 and the apolar regions of 2(H2A and H2B)] around which the double-stranded DNA helix is wound 1¾ time containing 146 base pairs.
In chromatin, the DNA extends as a continuous thread from nucleosome to nucleosome.
Each nucleosome bead is separated from the next by a region of linker DNA which is generally 54 base pair long and contains single H1 histone protein molecule.
Generally, DNA makes two complete turns around the histone octamers and these two turns (200 bp long) are sealed off by H1 molecules.
On average, nucleosomes repeat at intervals of about 200 nucleotides or base pairs. For example, a eukaryotic gene of 10,000 nucleotide pairs will be associated with 50 nucleosomes and each human cell with 6 x 109 DNA nucleotide pairs contains 3 x 107
The Folding of the DNA
The first step is the assembly of the DNA with a newly synthesized tetramer (H3-H4), are specifically modified (e.g. H4 is acetylated at Lys5 and Lysl2 (H3-H4)), to form a sub-nucleosomal particle, which is followed by the addition of two H2A-H2B dimers.
This produces a nucleosomal core particle consisting of 146 base pairs of DNA bind around the histone octamer. This core particle and the linker DNA together form the nucleosome.
The next step is the maturation step that requires ATP to establish regular spacing of the nucleosome cores to form the nucleo-filament.
During this step the newly incorporated histones are de-acetylated.
Next, the incorporation of linker histones is accompanied by folding of the nucleo-filament into the 30 nm fiber, the structure of which remains to be elucidated.
Two principal models exist- the solenoid model and the zig-zag.
Finally, further successive folding events lead to a high level of organization and specific domains in the nucleus.
McGinty, R. K., & Tan, S. (2014). Nucleosome structure and function. Chemical reviews, 115(6), 2255– doi:10.1021/cr500373h
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