Everything about Histone totally explained
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:
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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