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In biology, histones are the chief protein components of chromatin. They act as spools around which DNA winds, and they play a role in gene regulation. Without histones, the unwound DNA in chromosomes would be very long. For example, each human cell has about 1.8 meters of DNA, but wound on the histones it has about 90 millimeters of chromatin, which, when duplicated and condensed during mitosis, result in about 120 micrometers of chromosomes.

Classes

Six major histone classes are known: » * H1 (sometimes called the linker histone; also related to Histone H5.)


   * H2A » * H2B


   * H3 » * H4


   * Archaeal histones Two each of the class H2A, H2B, H3 and H4, so-called core histones, assemble to form one octameric nucleosome core particle by wrapping 146 base pairs of DNA around the protein spool in 1.65 left-handed super-helical turn. The linker histone H1 binds the nucleosome and the entry and exit sites of the DNA, thus locking the DNA into place and allowing the formation of higher order structure. The most basic such formation is the 10 nm fiber or beads on a string conformation. This involves the wrapping of DNA around nucleosomes with approximately 50 base pairs of DNA spaced between each nucleosome (also referred to as linker DNA). The assembled histones and DNA is called chromatin. Higher order structures include the 30 nm fiber (forming an irregular zigzag) and 100 nm fiber, these being the structures found in normal cells. During mitosis and meiosis, the condensed chromosomes are assembled through interactions between nucleosomes and other regulatory proteins.

Structure

The nucleosome core is formed of two H2A-H2B dimers and a H3-H4 tetramer, forming two nearly symmetrical halves by tertiary structure (C2 symmetry; one macromolecule is the mirror image of the other). Histone modifications act in diverse biological processes such as gene regulation, DNA repair and chromosome condensation (mitosis).
The common nomenclature of histone modifications is as follows:
  • The name of the histone (e.g H3)
  • The single letter amino acid abbreviation (for example K for Lysine) and the amino acid position in the protein
  • The type of modification (Me: methyl, P: phosphate, Ac: acetyl, Ub: ubiquitin) So H3K4me1 denotes the monomethylation of H3 on the 4th lysine from the start (N-terminal) of the protein.
       For a detailed example of histone modifications in transcription regulation see RNA polymerase control by chromatin structure and table.

    Influence on gene expression in mammalian cells:

    Type of modification
    H3K4 H3K9 H3K27 H3K79 H4K20 H2BK5
    monomethylation activation activation activation activation activation activation
    dimethylation activation
    trimethylations activation repression repression repressionactivation
    H3K9 H3K14
    acetylation activation activation

    History

    Histones were discovered in 1884 by Albrecht Kossel. The word "histone" dates from the late 19th century and is from the German "Histon", of uncertain origin: perhaps from Greek histanai or from histos. Until the early 1990s, histones were dismissed as merely packing material for nuclear DNA. During the early 1990s, the regulatory functions of histones were discovered.

    Conservation across species

    Histones are found in the nuclei of eukaryotic cells, and in certain Archaea, namely Euryarchaea, but not in bacteria. Archaeal histones may well resemble the evolutionary precursors to eukaryotic histones. Histone proteins are among the most highly conserved proteins in eukaryotes, emphasizing their important role in the biology of the nucleus.
    Core histones are highly conserved proteins, that is, there are very few differences among the amino acid sequences of the histone proteins of different species. Linker histone usually has more than one form within a species and is also less conserved than the core histones.
    There are some variant forms in some of the major classes. They share amino acid sequence homology and core structural similarity to a specific class of major histones but also have their own feature that's distinct from the major histones. These minor histones usually carry out specific functions of the chromatin metabolism. For example, histone H3-like CenpA is a histone only associated with centromere region of the chromosome. Histone H2A variant H2A.Z is associated with the promoters of actively transcribed genes and also involved in the formation of the heterochromatin. Another H2A variant H2A.X binds to the DNA with double strand breaks and marks the region undergoing DNA repair. Histone H3.3 is associated with the body of actively transcribed genes.

    Further Information

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