Histones

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Histones are the building blocks of Chromatin structure. In order for DNA to be packaged tightly enough to fit into a chromosome, it wraps around proteins called histones, located in the nucleus of a cell [1].

The importance of these proteins has been discussed by Alberts Et al. The author claims that within each human Nuclei, such hugh quantities of Histones exist, that, combined, their total weight would equal that of DNA itself. The value of Histones is further demonstrated when one considers its finction. Vital for 'wrapping' DNA they play a major role in producing the primary and arguably the most basic level of DNA structural units. There repeating units are tearmed Nucleosomes and are often referred to as 'Beads on a string'.

Histones, which is one of the two classes of DNA-binding proteins of chromatin, consists of five different types of proteins. These are H1, H2A, H2B, H3 and H4 and have unique properties from one another. These can be further regrouped into two major classes; Core and Linker:

  1. Core Histones - H3, H4, H2B and H2A.
  2. Linker Histone - H1.

Two of the core Histones (H3, H4, H2B, H2A) form the histone octamer core of the Nucleosome. On the other hand, H1, the linker histone, helps to form higher order structures.[2]The core histones are each made of a globular domain and a NH2-terminal end tail, which is arginine and leucine rich to give the tails a positive charge. The negative charge of the DNA and the positive charge of the amino acid residues attract each other and hold the chromatid together (much like glue) [3].

The histone octomer is made up of two dimers of H4/H3 and surrounded on either side by a H2A/H2B dimer. This dimer is capable of winding 147 base pairs of DNA around itself, in two left-handed loops, forming a structure known as a nucleosome. Each nucleosome is seperated by 20-30 base pairs of DNA, and can also be referred to as 'linker DNA' [4].

The H1 linker is reqruited once the DNA has been wound around the nucleosome and it's affinity is increased. This linker protein allows for the 10nm strand to be condensed further into a 30nm strand [5] (the structure is not 100% known, but it is believed to be a solanoid).

This highly efficient method of packaging DNA allows for around 2 meters of our genetic material to be condensed into a cell that is only a few microns across. However, this also poses a problem as the DNA becomes almost unaccessable for any gene transcription machinery.

The positive arginine and leucine residues on the NH2-terminal tails also provide a target for modulating the chromatid structure, in order to generate a more easily approchable DNA strand and to allow gene expression to take place. There are four major methods of chromatid structure modulation:

'1. Post translational Modification of Histones'

References

  1. http://en.citizendium.org/wiki/Histone
  2. Mathews et al. (2000); Biochemistry; 3rd Edition
  3. Lodish et al. (2008). Molecular Cell Biology. New York: W. H. Freeman and Company.
  4. White, Robert J. (2000). Gene transcription: mechanisms and control. Malden, MA: Blackwell Science.
  5. http://www.annualreviews.org/doi/full/10.1146/annurev.biophys.26.1.83
  6. Lodish et al. (2008). Molecular Cell Biology. New York: W. H. Freeman and Company.