A wikipedia of Dr. D'Adamo's research


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In biology, histones are the chief proteins of chromatin?. They act as spools around which DNA winds and they play a role in gene regulation. histones are found in the nuclei of [Eukaryote? Eukaryotic] cells. Bacteria do not have histones, but histones are found in certain Archaea, namely Euryarchaea. These archaeal histones may well resemble the evolutionary precursors to the [Eukaryote? Eukaryotic] histones. Histone proteins are among the most [Gene conservation? highly conserved] proteins in [eukaryote? eukaryotes], emphasizing the important role they play in the biology of the nucleus.


Six major histone classes are known:

  • H1 (sometimes called the linker histone or 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). 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 meiosis, through the combination of nucleosome interactions with other proteins, the chromosome is assembled. The assembled histones and DNA is called chromatin?.

Core histones are highly conserved proteins, meaning that very few changes can be found in the amino acid sequences when comparing the histone proteins from different species. Linker histone usually has more than one forms 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 posses their own feature that is 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 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.


Schematic representation of the assembly of the core histones into the nucleosome.

The nucleosome core is formed of two H2A-H2B dimers and two H3-H4 dimers, forming two nearly symmetrical halves by tertiary structure (C2 symmetry; one macromolecule is the mirror image of the other). The H2A-H2B and H3-H4 dimers themselves also show pseudodyad symmetry.

The 4 'core' histones (H2A, H2B, H3 and H4) are relatively similar in structure and are highly conserved through evolution, all featuring a 'helix turn helix turn helix' motif (which allows the easy dimerisation). They also share the feature of long 'tails' on one end of the amino acid structure - this being the location of post-transcriptional modification (see below).

In all, histones make five types of interactions with DNA:

  1. Helix-dipoles from alpha-helices in H2B, H3, and H4 cause a net positive charge to accumulate at the point of interaction with negatively charged phosphate groups on DNA.
  2. Hydrogen bonds between the DNA backbone and the amine group on the main chain of histone proteins.
  3. Nonpolar interactions between the histone and deoxyribose sugars on DNA.
  4. Salt links and hydrogen bonds between side chains of basic amino acids (especially lysine and arginine) and phosphate oxygens on DNA.
  5. Non-specific minor groove insertions of the H3 and H2B N-terminal tails into two minor grooves each on the DNA molecule.

The highly basic nature of histones, aside from facilitating DNA-histone interactions, contributes to the water solubility of histones.

histones are subject to posttranslational modification by enzymes primarily on their N-terminal tails, but also in their globular domains. Such modifications include methylation?, citrullination, acetylation, phosphorylation, Sumoylation, ubiquitination, and ADP-ribosylation. This affects their function of gene regulation (see functions).

In general, genes that are active have less bound histone, while inactive genes are highly associated with histones during interphase. It also appears that the structure of histones have been evolutionarily conserved, as any deleterious [Mutation? mutations] would be severely maladaptive.


Packing proteins

histones act as spools around which DNA winds. This enables the compaction necessary to fit the large genomes of [eukaryote? eukaryote]s inside cell nuclei: the compacted molecule is 50,000 times shorter than an unpacked molecule.

Histone modfications in chromatin regulation

Histones undergo posttranslational modifications which alter their interaction with DNA and nuclear proteins. The H3 and H4 histones have long tails protruding from the nucleosome which can be covalently modified at several places. Modifications of the tail include methylation?, acetylation, citrullination and phosphorylation. The core of the histones (H2A and H3) can also be modified. Combinations of modifications are thought to constitute a code, the so-called "histone code". Histone modifications act in diverse biological processes such as gene regulation, DNA repair and chromosome condensation (mitosis).

The common nomeclature of histone modifications is as follows:

  1. The name of the histone (e.g H3)
  2. The single letter amino acid abbreviation (e.g. K for Lysine) and the amino acid position in the protein
  3. The type of modification (Me: methyl, P: phosphate, Ac: acetyl, Ub: ubiquitin)

So H3K4Me denotes the methylation 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.


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.





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