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5.6:

The Nucleosome

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Molecular Biology
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JoVE Core Molecular Biology
The Nucleosome

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Proteins play a key role in determining the physical structure of a chromosome. The most abundant of these are small, positively charged proteins called histones. This positive charge allows them to tightly associate with the negatively charged DNA. During certain stages of the cell cycle, DNA is wound tightly around specific types of histones, forming structures called nucleosomes. Nucleosomes are often described as ‘beads’ on a ‘string’ of DNA. A nucleosome consists of a few key elements.  The first of these is an octamer of histone proteins, two molecules each of H2A, H2B, H3, and H4. Next, a nucleosome also has a 145 -147 bp length of DNA wrapped around the protein octamer nearly two times.  Together, the histone octamer and the DNA wound around it are known as a nucleosome core particle.  Each of the histones in the nucleosome core particle has a small, positively charged tail consisting of 11-27 amino acids.  The tails extend out from the nucleosome core particle and aid in keeping the negatively charged DNA and the histones associated. Furthermore, the histone tails can interact with tails from neighboring core particles, which facilitates DNA packaging.   A fifth type of histone, H1, plays a key role in nucleosome structure, though it is not part of the nucleosome core particle. H1 binds to the DNA where it joins and then leaves the octamer, acting as a clamp and keeping the DNA in place. Finally, the nucleosome also encompasses the stretch of linker DNA adjacent to the nucleosome core particle. The linker DNA that separates each core particle can vary in length, from about 30 to 40 base pairs, between cell types.  While the terms nucleosome and nucleosome core particle are often used interchangeably, the nucleosome actually refers to the nucleosome core particle and the adjacent linker DNA.  Altogether, nucleosomes are capable of reducing a long DNA molecule into a chromatin thread that is about one-third of its original length.

5.6:

The Nucleosome

DNA in a human cell is almost 2m long and it is packed inside a tiny nucleus that is only a few microns in diameter. The level of compaction of DNA inside the nucleus is astonishing. It is organized into several sequentially higher levels of compaction to fit into such a tiny space. The most compact form of DNA is a chromosome that can be seen under a microscope in a dividing cell.

DNA is wound twice around a protein complex called histone core, that consist of 8 histone proteins. This complex of DNA and histone protein is called the nucleosome, the fundamental and functional unit of DNA compaction. Nucleosomes can further coil around themselves into higher order compaction.

When the DNA is extracted from cells in low salt conditions and examined under a microscope, it resembles the beads on a string. The string represents the free DNA called "linker DNA," connecting the bead-like nucleosomes. If the DNA is isolated in physiological salt conditions (0.15 M KCl), it assumes a fiber-like form with 30 nm diameter that is bound to H1, a nonhistone protein. The H1 protein tightly binds to both the nucleosome and does not allow the DNA to slip.

Histones are highly conserved proteins

The amino acid sequences of core histone proteins are highly conserved between distantly related species. For example, the amino acid sequence of H3 histone between calf thymus and pea plant has only four amino acid differences.

Nonhistone proteins

Nucleosomes complex is also bound by a small proportion of nonhistone proteins, which help in maintaining the compaction and organizing long chromatin loops. Nonhistone proteins are also involved in the regulation of DNA replication and RNA synthesis.

Suggested Reading

  1. Molecular Cell Biology, Lodish, 8th edition, Pages 328-339
  2. Annunziato, A. "DNA packaging: nucleosomes and chromatin." Nature Education 1, no. 1 (2008): 26.