Nucleosome Model of Chromosome

Nucleosome Model of Chromosome

Nucleosome Model of Chromosome

  • 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 of Chromosome

Introduction

  • 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.

References

  1. McGinty, R. K., & Tan, S. (2014). Nucleosome structure and function. Chemical reviews115(6), 2255– doi:10.1021/cr500373h
  2. Verma, P. S., & Agrawal, V. K. (2006). Cell Biology, Genetics, Molecular Biology, Evolution & Ecology (1 ed.). S .Chand and company Ltd.
  3. Alberts, B., Johnson, A., Lewis, J., Raff, M., Roberts, K., & Walter, P. (2002). Molecular biology of the cell. New York: Garland Science.
  4. https://www.easybiologyclass.com/nucleosome-model-of-chromosomes-in-eukaryotes-short-notes/
  5. http://www.biologydiscussion.com/cell-biology/nucleosome-model/nucleosome-model-of-chromatin-assembly-cell-nucleus-biology/78886
  6. https://www.mechanobio.info/genome-regulation/what-are-nucleosomes/
  7. https://www.ncbi.nlm.nih.gov/pubmed/958895

Nucleosome Model of Chromosome

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