Histone
Encyclopedia
In biology
Biology
Biology is a natural science concerned with the study of life and living organisms, including their structure, function, growth, origin, evolution, distribution, and taxonomy. Biology is a vast subject containing many subdivisions, topics, and disciplines...

, histones are highly alkaline protein
Protein
Proteins are biochemical compounds consisting of one or more polypeptides typically folded into a globular or fibrous form, facilitating a biological function. A polypeptide is a single linear polymer chain of amino acids bonded together by peptide bonds between the carboxyl and amino groups of...

s found in eukaryotic
Eukaryote
A eukaryote is an organism whose cells contain complex structures enclosed within membranes. Eukaryotes may more formally be referred to as the taxon Eukarya or Eukaryota. The defining membrane-bound structure that sets eukaryotic cells apart from prokaryotic cells is the nucleus, or nuclear...

 cell nuclei that package and order the DNA
DNA
Deoxyribonucleic acid is a nucleic acid that contains the genetic instructions used in the development and functioning of all known living organisms . The DNA segments that carry this genetic information are called genes, but other DNA sequences have structural purposes, or are involved in...

 into structural units called nucleosomes. They are the chief protein components of chromatin
Chromatin
Chromatin is the combination of DNA and proteins that make up the contents of the nucleus of a cell. The primary functions of chromatin are; to package DNA into a smaller volume to fit in the cell, to strengthen the DNA to allow mitosis and meiosis and prevent DNA damage, and to control gene...

, acting as spools around which DNA winds, and play a role in gene regulation. Without histones, the unwound DNA in chromosomes would be very long (a length to width ratio of more than 10 million to one in human DNA). For example, each human cell has about 1.8 meters of DNA, but wound on the histones it has about 90 micrometers (0.09 mm) of chromatin, which, when duplicated and condensed during mitosis
Mitosis
Mitosis is the process by which a eukaryotic cell separates the chromosomes in its cell nucleus into two identical sets, in two separate nuclei. It is generally followed immediately by cytokinesis, which divides the nuclei, cytoplasm, organelles and cell membrane into two cells containing roughly...

, result in about 120 micrometers of chromosome
Chromosome
A chromosome is an organized structure of DNA and protein found in cells. It is a single piece of coiled DNA containing many genes, regulatory elements and other nucleotide sequences. Chromosomes also contain DNA-bound proteins, which serve to package the DNA and control its functions.Chromosomes...

s.

Classes

Five major classes of histones exist: H1/H5, H2A, H2B, H3, and H4. Histones H2A, H2B, H3 and H4 are known as the core histones, while histones H1 and H5 are known as the linker histones.

Two of each of the core histones assemble to form one octameric nucleosome
Nucleosome
Nucleosomes are the basic unit of DNA packaging in eukaryotes, consisting of a segment of DNA wound around a histone protein core. This structure is often compared to thread wrapped around a spool....

 core particle, and 147 base pairs of DNA wrap around this core particle 1.65 times in a 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
DNA
Deoxyribonucleic acid is a nucleic acid that contains the genetic instructions used in the development and functioning of all known living organisms . The DNA segments that carry this genetic information are called genes, but other DNA sequences have structural purposes, or are involved in...

 separating each pair of nucleosome
Nucleosome
Nucleosomes are the basic unit of DNA packaging in eukaryotes, consisting of a segment of DNA wound around a histone protein core. This structure is often compared to thread wrapped around a spool....

s (also referred to as linker DNA
DNA
Deoxyribonucleic acid is a nucleic acid that contains the genetic instructions used in the development and functioning of all known living organisms . The DNA segments that carry this genetic information are called genes, but other DNA sequences have structural purposes, or are involved in...

). The assembled histones and DNA
DNA
Deoxyribonucleic acid is a nucleic acid that contains the genetic instructions used in the development and functioning of all known living organisms . The DNA segments that carry this genetic information are called genes, but other DNA sequences have structural purposes, or are involved in...

 is called chromatin
Chromatin
Chromatin is the combination of DNA and proteins that make up the contents of the nucleus of a cell. The primary functions of chromatin are; to package DNA into a smaller volume to fit in the cell, to strengthen the DNA to allow mitosis and meiosis and prevent DNA damage, and to control gene...

. 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 chromosome
Chromosome
A chromosome is an organized structure of DNA and protein found in cells. It is a single piece of coiled DNA containing many genes, regulatory elements and other nucleotide sequences. Chromosomes also contain DNA-bound proteins, which serve to package the DNA and control its functions.Chromosomes...

s are assembled through interactions between nucleosomes and other regulatory proteins.

The following is a list of human histone proteins:
Super family Family Subfamily Members
Linker
H1
Histone H1
Histone H1 is one of the five main histone protein families which are components of chromatin in eukaryotic cells. Though highly conserved, it is nevertheless the most variable histone in sequence across species.- Structure :...

H1F H1F0
H1F0
H1 histone family, member 0 is a member of the histone family of nuclear proteins which are a component of chromatin. In humans, this protein is encoded by the H1F0 gene....

, H1FNT
H1FNT
H1 histone family, member N, testis-specific is a member of the histone family of nuclear proteins which are a component of chromatin. In humans, this protein is encoded by the H1FNT gene....

, H1FOO
H1FOO
Histone H1oo is a protein that in humans is encoded by the H1FOO gene.- Function :Histones are basic nuclear proteins that are responsible for the nucleosome structure of the chromosomal fiber in eukaryotes. Nucleosomes consist of approximately 146 bp of DNA wrapped around a histone octamer...

, H1FX
H1FX
Histone H1x is a protein that in humans is encoded by the H1FX gene.-Further reading:...

H1H1 HIST1H1A
HIST1H1A
Histone H1.1 is a protein that in humans is encoded by the HIST1H1A gene.-Further reading:...

, HIST1H1B
HIST1H1B
Histone H1.5 is a protein that in humans is encoded by the HIST1H1B gene.-Further reading:...

, HIST1H1C
HIST1H1C
Histone H1.2 is a protein that in humans is encoded by the HIST1H1C gene.-Further reading:...

, HIST1H1D
HIST1H1D
Histone H1.3 is a protein that in humans is encoded by the HIST1H1D gene.-Further reading:...

, HIST1H1E
HIST1H1E
Histone H1.4 is a protein that in humans is encoded by the HIST1H1E gene.-Further reading:...

, HIST1H1T
HIST1H1T
Histone H1t is a protein that in humans is encoded by the HIST1H1T gene.-Further reading:...

Core
H2A
Histone H2A
Histone H2A is one of the 5 main histone proteins involved in the structure of chromatin in eukaryotic cells. Featuring a main globular domain and a long N terminal tail, H2A is involved with the structure of the nucleosomes of the 'beads on a string' structure.Other histone proteins...

H2AF H2AFB1
H2AFB1
Histone H2A-Bbd type 1 also known as H2A Barr body-deficient is a histone protein that in humans is encoded by the H2AFB1 gene .- Function :...

, H2AFB2
H2AFB2
Histone H2A-Bbd type 2/3 also known as H2A Barr body-deficient is a histone protein that in humans is encoded by the H2AFB2 gene .- Function :...

, H2AFB3, H2AFJ
H2AFJ
Histone H2A.J is a protein that in humans is encoded by the H2AFJ gene.-Further reading:...

, H2AFV
H2AFV
Histone H2A.V is a protein that in humans is encoded by the H2AFV gene.-Further reading:...

, H2AFX
H2AFX
H2AX is one of several genes coding for histone H2A. In humans and other eukaryotes, the DNA is wrapped around histone-groups, consisting of core histones H2A, H2B, H3 and H4. Thus, the H2AX contributes to the histone-formation and therefore the structure of DNA.H2AX becomes phosphorylated on...

, H2AFY
H2AFY
Core histone macro-H2A.1 is a protein that in humans is encoded by the H2AFY gene.-Further reading:...

, H2AFY2
H2AFY2
Core histone macro-H2A.2 is a protein that in humans is encoded by the H2AFY2 gene.-Further reading:...

, H2AFZ
H2AFZ
Histone H2A.Z is a protein that in humans is encoded by the H2AFZ gene.-Further reading:...

H2A1 HIST1H2AA
HIST1H2AA
Histone H2A type 1-A is a protein that in humans is encoded by the HIST1H2AA gene.-Further reading:...

, HIST1H2AB
HIST1H2AB
Histone H2A type 1-B/E is a protein that in humans is encoded by the HIST1H2AB gene.-Further reading:...

, HIST1H2AC
HIST1H2AC
Histone H2A type 1-C is a protein that in humans is encoded by the HIST1H2AC gene.-Further reading:...

, HIST1H2AD
HIST1H2AD
Histone H2A type 1-D is a protein that in humans is encoded by the HIST1H2AD gene.-Further reading:...

, HIST1H2AE
HIST1H2AE
Histone H2A type 1-B/E is a protein that in humans is encoded by the HIST1H2AE gene.-Further reading:...

, HIST1H2AG
HIST1H2AG
Histone H2A type 1 is a protein that in humans is encoded by the HIST1H2AG gene.-Further reading:...

, HIST1H2AI
HIST1H2AI
Histone H2A type 1 is a protein that in humans is encoded by the HIST1H2AI gene.-Further reading:...

, HIST1H2AJ
HIST1H2AJ
Histone H2A type 1-J is a protein that in humans is encoded by the HIST1H2AJ gene.-Further reading:...

, HIST1H2AK
HIST1H2AK
Histone H2A type 1 is a protein that in humans is encoded by the HIST1H2AK gene.-Further reading:...

, HIST1H2AL
HIST1H2AL
Histone H2A type 1 is a protein that in humans is encoded by the HIST1H2AL gene.-Further reading:...

, HIST1H2AM
HIST1H2AM
Histone H2A type 1 is a protein that in humans is encoded by the HIST1H2AM gene.-Further reading:...

H2A2 HIST2H2AA3
HIST2H2AA3
Histone H2A type 2-A is a protein that in humans is encoded by the HIST2H2AA3 gene.-Further reading:...

, HIST2H2AC
HIST2H2AC
Histone H2A type 2-C is a protein that in humans is encoded by the HIST2H2AC gene.-Further reading:...

H2B
Histone H2B
Histone H2B is one of the 5 main histone proteins involved in the structure of chromatin in eukaryotic cells. Featuring a main globular domain and a long N terminal tail H2B is involved with the structure of the nucleosomes of the 'beads on a string' structure.See nucleosome, histone and...

H2BF H2BFM, H2BFO, H2BFS
H2BFS
Histone H2B type F-S is a protein that in humans is encoded by the H2BFS gene.-Further reading:...

, H2BFWT
H2B1 HIST1H2BA
HIST1H2BA
Histone H2B type 1-A is a protein that in humans is encoded by the HIST1H2BA gene.-Further reading:...

, HIST1H2BB
HIST1H2BB
Histone H2B type 1-B is a protein that in humans is encoded by the HIST1H2BB gene.-Further reading:...

, HIST1H2BC, HIST1H2BD
HIST1H2BD
Histone H2B type 1-D is a protein that in humans is encoded by the HIST1H2BD gene.-Further reading:...

, HIST1H2BE
HIST1H2BE
Histone H2B type 1-C/E/F/G/I is a protein that in humans is encoded by the HIST1H2BE gene.-Further reading:...

, HIST1H2BF
HIST1H2BF
Histone H2B type 1-C/E/F/G/I is a protein that in humans is encoded by the HIST1H2BF gene.-Further reading:...

, HIST1H2BG
HIST1H2BG
Histone H2B type 1-C/E/F/G/I is a protein that in humans is encoded by the HIST1H2BG gene.-Further reading:...

, HIST1H2BH
HIST1H2BH
Histone H2B type 1-H is a protein that in humans is encoded by the HIST1H2BH gene.-Further reading:...

, HIST1H2BI
HIST1H2BI
Histone H2B type 1-C/E/F/G/I is a protein that in humans is encoded by the HIST1H2BI gene.-Further reading:...

, HIST1H2BJ
HIST1H2BJ
Histone H2B type 1-J is a protein that in humans is encoded by the HIST1H2BJ gene.-Further reading:...

, HIST1H2BK
HIST1H2BK
Histone H2B type 1-K is a protein that in humans is encoded by the HIST1H2BK gene.-Further reading:...

, HIST1H2BL
HIST1H2BL
Histone H2B type 1-L is a protein that in humans is encoded by the HIST1H2BL gene.-Further reading:...

, HIST1H2BM
HIST1H2BM
Histone H2B type 1-M is a protein that in humans is encoded by the HIST1H2BM gene.-Further reading:...

, HIST1H2BN
HIST1H2BN
Histone H2B type 1-N is a protein that in humans is encoded by the HIST1H2BN gene.-Further reading:...

, HIST1H2BO
HIST1H2BO
Histone H2B type 1-O is a protein that in humans is encoded by the HIST1H2BO gene.-Further reading:...

H2B2 HIST2H2BE
HIST2H2BE
Histone H2B type 2-E is a protein that in humans is encoded by the HIST2H2BE gene.-Further reading:...

H3
Histone H3
Histone H3 is one of the five main histone proteins involved in the structure of chromatin in eukaryotic cells. Featuring a main globular domain and a long N-terminal tail, H3 is involved with the structure of the nucleosomes of the 'beads on a string' structure...

H3A1 HIST1H3A
HIST1H3A
Histone H3.1 is a protein that in humans is encoded by the HIST1H3A gene.-Further reading:...

, HIST1H3B
HIST1H3B
Histone H3.1 is a protein that in humans is encoded by the HIST1H3B gene.-Further reading:...

, HIST1H3C
HIST1H3C
Histone H3.1 is a protein that in humans is encoded by the HIST1H3C gene.-Further reading:...

, HIST1H3D
HIST1H3D
Histone H3.1 is a protein that in humans is encoded by the HIST1H3D gene.-Further reading:...

, HIST1H3E
HIST1H3E
Histone H3.1 is a protein that in humans is encoded by the HIST1H3E gene.-Further reading:...

, HIST1H3F
HIST1H3F
Histone H3.1 is a protein that in humans is encoded by the HIST1H3F gene.-Further reading:...

, HIST1H3G
HIST1H3G
Histone H3.1 is a protein that in humans is encoded by the HIST1H3G gene.-Further reading:...

, HIST1H3H
HIST1H3H
Histone H3.1 is a protein that in humans is encoded by the HIST1H3H gene.-Further reading:...

, HIST1H3I
HIST1H3I
Histone H3.1 is a protein that in humans is encoded by the HIST1H3I gene.-Further reading:...

, HIST1H3J
HIST1H3J
Histone H3.1 is a protein that in humans is encoded by the HIST1H3J gene.-Further reading:...

H3A2 HIST2H3C
HIST2H3C
Histone H3.2 is a protein that in humans is encoded by the HIST2H3C gene.-Further reading:...

H3A3 HIST3H3
HIST3H3
Histone H3.1t is a protein that in humans is encoded by the HIST3H3 gene.-Further reading:...

H4
Histone H4
Histone H4 is one of the 5 main histone proteins involved in the structure of chromatin in eukaryotic cells. Featuring a main globular domain and a long N terminal tail, H4 is a structural component of the nucleosome, and is subject to covalent modification, including acetylation and methylation,...

H41 HIST1H4A
HIST1H4A
Histone H4 is a protein that in humans is encoded by the HIST1H4A gene.-Further reading:...

, HIST1H4B
HIST1H4B
Histone H4 is a protein that in humans is encoded by the HIST1H4B gene.-Further reading:...

, HIST1H4C
HIST1H4C
Histone H4 is a protein that in humans is encoded by the HIST1H4C gene.-Further reading:...

, HIST1H4D
HIST1H4D
Histone H4 is a protein that in humans is encoded by the HIST1H4D gene.-Further reading:...

, HIST1H4E
HIST1H4E
Histone H4 is a protein that in humans is encoded by the HIST1H4E gene.-Further reading:...

, HIST1H4F
HIST1H4F
Histone H4 is a protein that in humans is encoded by the HIST1H4F gene.-Further reading:...

, HIST1H4G
HIST1H4G
Histone H4-like protein type G is a protein that in humans is encoded by the HIST1H4G gene.-Further reading:...

, HIST1H4H
HIST1H4H
Histone H4 is a protein that in humans is encoded by the HIST1H4H gene.-Further reading:...

, HIST1H4I
HIST1H4I
Histone H4 is a protein that in humans is encoded by the HIST1H4I gene.-Further reading:...

, HIST1H4J, HIST1H4K
HIST1H4K
Histone H4 is a protein that in humans is encoded by the HIST1H4K gene.-Further reading:...

, HIST1H4L
HIST1H4L
Histone H4 is a protein that in humans is encoded by the HIST1H4L gene.-Further reading:...

H44 HIST4H4
HIST4H4
Histone H4 is a protein that in humans is encoded by the HIST4H4 gene.-Further reading:...


Structure

The nucleosome
Nucleosome
Nucleosomes are the basic unit of DNA packaging in eukaryotes, consisting of a segment of DNA wound around a histone protein core. This structure is often compared to thread wrapped around a spool....

 core is formed of two H2A-H2B dimers
Protein dimer
In biochemistry, a dimer is a macromolecular complex formed by two, usually non-covalently bound, macromolecules like proteins or nucleic acids...

 and a H3-H4 tetramer, forming two nearly symmetrical
Symmetry
Symmetry generally conveys two primary meanings. The first is an imprecise sense of harmonious or aesthetically pleasing proportionality and balance; such that it reflects beauty or perfection...

 halves by tertiary structure
Tertiary structure
In biochemistry and molecular biology, the tertiary structure of a protein or any other macromolecule is its three-dimensional structure, as defined by the atomic coordinates.-Relationship to primary structure:...

 (C2
Point groups in three dimensions
In geometry, a point group in three dimensions is an isometry group in three dimensions that leaves the origin fixed, or correspondingly, an isometry group of a sphere. It is a subgroup of the orthogonal group O, the group of all isometries that leave the origin fixed, or correspondingly, the group...

 symmetry; one macromolecule
Macromolecule
A macromolecule is a very large molecule commonly created by some form of polymerization. In biochemistry, the term is applied to the four conventional biopolymers , as well as non-polymeric molecules with large molecular mass such as macrocycles...

 is the mirror image of the other). The H2A-H2B dimers and H3-H4 tetramer also show pseudodyad symmetry. The 4 'core' histones (H2A, H2B, H3 and H4) are relatively similar in structure and are highly conserved through evolution
Evolution
Evolution is any change across successive generations in the heritable characteristics of biological populations. Evolutionary processes give rise to diversity at every level of biological organisation, including species, individual organisms and molecules such as DNA and proteins.Life on Earth...

, 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
Amino acid
Amino acids are molecules containing an amine group, a carboxylic acid group and a side-chain that varies between different amino acids. The key elements of an amino acid are carbon, hydrogen, oxygen, and nitrogen...

 structure - this being the location of post-translational modification (see below).

It has been proposed that histone proteins are evolutionarily related to the helical part of the extended AAA+ ATPase domain, the C-domain, and to the N-terminal substrate recognition domain of Clp/Hsp100 proteins. Despite the differences in their topology, these three folds share a homologous helix-strand-helix (HSH) motif.
Using an electron paramagnetic resonance
Electron paramagnetic resonance
Electron paramagnetic resonance or electron spin resonance spectroscopyis a technique for studying chemical species that have one or more unpaired electrons, such as organic and inorganic free radicals or inorganic complexes possessing a transition metal ion...

 spin-labeling technique, British researchers measured the distances between the spools around which eukaryotic cells wind their DNA. They determined the spacings range from 59 to 70 Å.

In all, histones make five types of interactions with DNA:
  • Helix-dipoles from alpha-helices
    Alpha helix
    A common motif in the secondary structure of proteins, the alpha helix is a right-handed coiled or spiral conformation, in which every backbone N-H group donates a hydrogen bond to the backbone C=O group of the amino acid four residues earlier...

     in H2B, H3, and H4 cause a net positive charge to accumulate at the point of interaction with negatively charged phosphate
    Phosphate
    A phosphate, an inorganic chemical, is a salt of phosphoric acid. In organic chemistry, a phosphate, or organophosphate, is an ester of phosphoric acid. Organic phosphates are important in biochemistry and biogeochemistry or ecology. Inorganic phosphates are mined to obtain phosphorus for use in...

     groups on DNA
  • Hydrogen bonds between the DNA backbone and the amide group on the main chain of histone proteins
  • Nonpolar interactions between the histone and deoxyribose
    Deoxyribose
    Deoxyribose, more, precisely 2-deoxyribose, is a monosaccharide with idealized formula H---3-H. Its name indicates that it is a deoxy sugar, meaning that it is derived from the sugar ribose by loss of an oxygen atom...

     sugars on DNA
  • Salt bridges and hydrogen bonds between side chains of basic amino acids (especially lysine
    Lysine
    Lysine is an α-amino acid with the chemical formula HO2CCH4NH2. It is an essential amino acid, which means that the human body cannot synthesize it. Its codons are AAA and AAG....

     and arginine
    Arginine
    Arginine is an α-amino acid. The L-form is one of the 20 most common natural amino acids. At the level of molecular genetics, in the structure of the messenger ribonucleic acid mRNA, CGU, CGC, CGA, CGG, AGA, and AGG, are the triplets of nucleotide bases or codons that codify for arginine during...

    ) and phosphate oxygens on DNA
  • 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 their water solubility.

Histones are subject to post translational modification by enzymes primarily on their N-terminal tails, but also in their globular domains. Such modifications include methylation
Methylation
In the chemical sciences, methylation denotes the addition of a methyl group to a substrate or the substitution of an atom or group by a methyl group. Methylation is a form of alkylation with, to be specific, a methyl group, rather than a larger carbon chain, replacing a hydrogen atom...

, citrullination
Citrullination
Citrullination or deimination is the term used for the post-translational modification of the amino acid arginine in a protein into the amino acid citrulline. This reaction, shown below, is performed by enzymes called peptidylarginine deiminases...

, acetylation
Acetylation
Acetylation describes a reaction that introduces an acetyl functional group into a chemical compound...

, phosphorylation
Phosphorylation
Phosphorylation is the addition of a phosphate group to a protein or other organic molecule. Phosphorylation activates or deactivates many protein enzymes....

, SUMOylation
SUMO protein
Small Ubiquitin-like Modifier or SUMO proteins are a family of small proteins that are covalently attached to and detached from other proteins in cells to modify their function...

, ubiquitin
Ubiquitin
Ubiquitin is a small regulatory protein that has been found in almost all tissues of eukaryotic organisms. Among other functions, it directs protein recycling.Ubiquitin can be attached to proteins and label them for destruction...

ation, and ADP-ribosylation
ADP-ribosylation
ADP-ribosylation is the addition of one or more ADP-ribose moieties to a protein. These reactions are involved in cell signaling and the control of many cell processes, including DNA repair and apoptosis.-ADP-ribosylation enzymes:...

. This affects their function of gene regulation (see functions).

In general, gene
Gene
A gene is a molecular unit of heredity of a living organism. It is a name given to some stretches of DNA and RNA that code for a type of protein or for an RNA chain that has a function in the organism. Living beings depend on genes, as they specify all proteins and functional RNA chains...

s that are active have less bound histone, while inactive genes are highly associated with histones during interphase
Interphase
Interphase is the phase of the cell cycle in which the cell spends the majority of its time and performs the majority of its purposes including preparation for cell division. In preparation for cell division, it increases its size and makes a copy of its DNA...

. It also appears that the structure of histones has been evolution
Evolution
Evolution is any change across successive generations in the heritable characteristics of biological populations. Evolutionary processes give rise to diversity at every level of biological organisation, including species, individual organisms and molecules such as DNA and proteins.Life on Earth...

arily conserved, as any deleterious mutations would be severely maladaptive.

Compacting DNA strands

Histones act as spools around which DNA winds. This enables the compaction necessary to fit the large genome
Genome
In modern molecular biology and genetics, the genome is the entirety of an organism's hereditary information. It is encoded either in DNA or, for many types of virus, in RNA. The genome includes both the genes and the non-coding sequences of the DNA/RNA....

s of eukaryotes inside cell nuclei: the compacted molecule is 40,000 times shorter than an unpacked molecule.

Chromatin regulation

Histones undergo posttranslational modification
Posttranslational modification
Posttranslational modification is the chemical modification of a protein after its translation. It is one of the later steps in protein biosynthesis, and thus gene expression, for many proteins....

s that alter their interaction with DNA
DNA
Deoxyribonucleic acid is a nucleic acid that contains the genetic instructions used in the development and functioning of all known living organisms . The DNA segments that carry this genetic information are called genes, but other DNA sequences have structural purposes, or are involved in...

 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
Methylation
In the chemical sciences, methylation denotes the addition of a methyl group to a substrate or the substitution of an atom or group by a methyl group. Methylation is a form of alkylation with, to be specific, a methyl group, rather than a larger carbon chain, replacing a hydrogen atom...

, acetylation
Acetylation
Acetylation describes a reaction that introduces an acetyl functional group into a chemical compound...

, phosphorylation
Phosphorylation
Phosphorylation is the addition of a phosphate group to a protein or other organic molecule. Phosphorylation activates or deactivates many protein enzymes....

, ubiquitination, SUMOylation, citrullination
Citrullination
Citrullination or deimination is the term used for the post-translational modification of the amino acid arginine in a protein into the amino acid citrulline. This reaction, shown below, is performed by enzymes called peptidylarginine deiminases...

, and ADP-ribosylation. The core of the histones H2A, H2B, and H3 can also be modified. Combinations of modifications are thought to constitute a code, the so-called "histone code
Histone code
The histone code is a hypothesis that the transcription of genetic information encoded in DNA is in part regulated by chemical modifications to histone proteins, primarily on their unstructured ends. Together with similar modifications such as DNA methylation it is part of the epigenetic code...

". Histone modifications act in diverse biological processes such as gene regulation, DNA repair
DNA repair
DNA repair refers to a collection of processes by which a cell identifies and corrects damage to the DNA molecules that encode its genome. In human cells, both normal metabolic activities and environmental factors such as UV light and radiation can cause DNA damage, resulting in as many as 1...

, chromosome condensation (mitosis
Mitosis
Mitosis is the process by which a eukaryotic cell separates the chromosomes in its cell nucleus into two identical sets, in two separate nuclei. It is generally followed immediately by cytokinesis, which divides the nuclei, cytoplasm, organelles and cell membrane into two cells containing roughly...

) and spermatogenesis
Spermatogenesis
Spermatogenesis is the process by which male primary germ cells undergo division, and produce a number of cells termed spermatogonia, from which the primary spermatocytes are derived. Each primary spermatocyte divides into two secondary spermatocytes, and each secondary spermatocyte into two...

 (meiosis
Meiosis
Meiosis is a special type of cell division necessary for sexual reproduction. The cells produced by meiosis are gametes or spores. The animals' gametes are called sperm and egg cells....

).

The common nomenclature of histone modifications is:
  • The name of the histone (e.g., H3)
  • The single-letter amino acid
    Amino acid
    Amino acids are molecules containing an amine group, a carboxylic acid group and a side-chain that varies between different amino acids. The key elements of an amino acid are carbon, hydrogen, oxygen, and nitrogen...

     abbreviation (e.g., K for Lysine
    Lysine
    Lysine is an α-amino acid with the chemical formula HO2CCH4NH2. It is an essential amino acid, which means that the human body cannot synthesize it. Its codons are AAA and AAG....

    ) and the amino acid position in the protein
  • The type of modification (Me: methyl, P: phosphate
    Phosphate
    A phosphate, an inorganic chemical, is a salt of phosphoric acid. In organic chemistry, a phosphate, or organophosphate, is an ester of phosphoric acid. Organic phosphates are important in biochemistry and biogeochemistry or ecology. Inorganic phosphates are mined to obtain phosphorus for use in...

    , Ac: acetyl
    Acetyl
    In organic chemistry, acetyl is a functional group, the acyl with chemical formula COCH3. It is sometimes represented by the symbol Ac . The acetyl group contains a methyl group single-bonded to a carbonyl...

    , Ub: ubiquitin
    Ubiquitin
    Ubiquitin is a small regulatory protein that has been found in almost all tissues of eukaryotic organisms. Among other functions, it directs protein recycling.Ubiquitin can be attached to proteins and label them for destruction...

    )


So H3K4me1 denotes the monomethylation of the 4th residue (a lysine) from the start (i.e., the N-terminal) of the H3 protein.

Examples of histone modifications in transcription regulation include:
Type of
modification
Histone
H3K4 H3K9 H3K14 H3K27 H3K79 H4K20 H2BK5
mono-methylation
Methylation
In the chemical sciences, methylation denotes the addition of a methyl group to a substrate or the substitution of an atom or group by a methyl group. Methylation is a form of alkylation with, to be specific, a methyl group, rather than a larger carbon chain, replacing a hydrogen atom...

activation activation activation activation activation activation
di-methylation repression repression activation
tri-methylation activation repression repression activation,
repression
repression
acetylation
Acetylation
Acetylation describes a reaction that introduces an acetyl functional group into a chemical compound...

activation activation

History

Histones were discovered in 1884 by Albrecht Kossel
Albrecht Kossel
Ludwig Karl Martin Leonhard Albrecht Kossel was a German biochemist and pioneer in the study of genetics. He was awarded the Nobel Prize for Physiology or Medicine in 1910 for his work in determining the chemical composition of nucleic acids, the genetic substance of biological cells.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 by most as inert packing material for eukaryotic nuclear DNA, based in part on the "ball and stick" models of Mark Ptashne
Mark Ptashne
Mark Ptashne is a molecular biologist and violinist. He currently holds the Ludwig Chair of Molecular Biology at Memorial Sloan–Kettering Cancer Center in New York...

 and others who believed that transcription was activated by protein-DNA and protein-protein interactions on largely naked DNA templates, as is the case in bacteria. During the 1980s, work by Michael Grunstein
Michael Grunstein
Michael Grunstein is a Distinguished Professor of Biological Chemistry at the Geffen School of Medicine at UCLA.He obtained his Bachelor of Science degree from McGill University in Montreal, and his PhD from the University of Edinburgh, Scotland...

  demonstrated that eukaryotic histones repress gene transcription, and that the function of transcriptional activators is to overcome this repression. It is now known that histones play both positive and negative roles in gene expression, forming the basis of the histone code
Histone code
The histone code is a hypothesis that the transcription of genetic information encoded in DNA is in part regulated by chemical modifications to histone proteins, primarily on their unstructured ends. Together with similar modifications such as DNA methylation it is part of the epigenetic code...

.

The discovery of the H5 histone appears to date back to 1970s, and in classification it has been grouped with H1.

Conservation across species

Histones are found in the nuclei of eukaryotic
Eukaryote
A eukaryote is an organism whose cells contain complex structures enclosed within membranes. Eukaryotes may more formally be referred to as the taxon Eukarya or Eukaryota. The defining membrane-bound structure that sets eukaryotic cells apart from prokaryotic cells is the nucleus, or nuclear...

 cells
Cell (biology)
The cell is the basic structural and functional unit of all known living organisms. It is the smallest unit of life that is classified as a living thing, and is often called the building block of life. The Alberts text discusses how the "cellular building blocks" move to shape developing embryos....

, and in certain Archaea
Archaea
The Archaea are a group of single-celled microorganisms. A single individual or species from this domain is called an archaeon...

, namely Euryarchaea
Euryarchaeota
In the taxonomy of microorganisms, the Euryarchaeota are a phylum of the Archaea.The Euryarchaeota include the methanogens, which produce methane and are often found in intestines, the halobacteria, which survive extreme concentrations of salt, and some extremely thermophilic aerobes and anaerobes...

, but not in bacteria
Bacteria
Bacteria are a large domain of prokaryotic microorganisms. Typically a few micrometres in length, bacteria have a wide range of shapes, ranging from spheres to rods and spirals...

. The unicellular algae known as dinoflagellates are the only eukaryotes that completely lack histones.

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. In contrast mature sperm cells largely use protamines to package their genomic DNA, most likely because this allows them to achieve an even higher packaging ratio.

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 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 associated with only the centromere
Centromere
A centromere is a region of DNA typically found near the middle of a chromosome where two identical sister chromatids come closest in contact. It is involved in cell division as the point of mitotic spindle attachment...

 region of the chromosome. Histone H2A variant H2A.Z is associated with the promoters of actively transcribed genes and also involved in the prevention of the spread of silent heterochromatin
Heterochromatin
Heterochromatin is a tightly packed form of DNA, which comes in different varieties. These varieties lie on a continuum between the two extremes of constitutive and facultative heterochromatin...

 . Furthermore, H2A.Z has roles in chromatin for genome stability . Another H2A variant H2A.X binds to the DNA with double-strand breaks and marks the region undergoing DNA repair
DNA repair
DNA repair refers to a collection of processes by which a cell identifies and corrects damage to the DNA molecules that encode its genome. In human cells, both normal metabolic activities and environmental factors such as UV light and radiation can cause DNA damage, resulting in as many as 1...

. Histone H3.3 is associated with the body of actively transcribed genes.

See also

  • Nucleosome
    Nucleosome
    Nucleosomes are the basic unit of DNA packaging in eukaryotes, consisting of a segment of DNA wound around a histone protein core. This structure is often compared to thread wrapped around a spool....

  • Chromatin
    Chromatin
    Chromatin is the combination of DNA and proteins that make up the contents of the nucleus of a cell. The primary functions of chromatin are; to package DNA into a smaller volume to fit in the cell, to strengthen the DNA to allow mitosis and meiosis and prevent DNA damage, and to control gene...

  • Histone-Modifying Enzymes
    Histone-Modifying Enzymes
    The packaging of the eukaryotic genome into highly condensed chromatin makes it inaccessible to the factors required for gene transcription, DNA replication, recombination and repair. Eukaryotes have developed intricate mechanisms to overcome this repressive barrier imposed by the chromatin...

  • Histone deacetylase
    Histone deacetylase
    Histone deacetylases are a class of enzymes that remove acetyl groups from an ε-N-acetyl lysine amino acid on a histone. This is important because DNA is wrapped around histones, and DNA expression is regulated by acetylation and de-acetylation. Its action is opposite to that of histone...

    s
  • PRMT4 pathway
    PRMT4 pathway
    Protein arginine N-methyltransferase-4 methylation of arginine residues within proteins plays a critical key role in transcriptional regulation . PRMT4 binds to the classes of transcriptional activators known as p160 and CBP/p300. The modified forms of these proteins are involved in stimulation of...

  • Gene silencing
    Gene silencing
    Gene silencing is a general term describing epigenetic processes of gene regulation. The term gene silencing is generally used to describe the "switching off" of a gene by a mechanism other than genetic modification...

  • Genetics
    Genetics
    Genetics , a discipline of biology, is the science of genes, heredity, and variation in living organisms....

  • Histone methyltransferase
    Histone methyltransferase
    Histone methyltransferases are enzymes, histone-lysine N-methyltransferase and histone-arginine N-methyltransferase, that catalyze the transfer of one to three methyl groups from the cofactor S-Adenosyl methionine to lysine and arginine residues of histone proteins...

  • Histone acetyltransferase
    Histone acetyltransferase
    Histone acetyltransferases are enzymes that acetylate conserved lysine amino acids on histone proteins by transferring an acetyl group from acetyl CoA to form ε-N-acetyl lysine....


External links

  • Chromatin, Histones & Cathepsin; PMAP The Proteolysis Map
    The Proteolysis Map
    The Proteolysis MAP is an integrated web resource focused on proteases.-Rationale:PMAP is to aid the protease researchers in reasoning about proteolytic networks and metabolic pathways.-History and funding:...

    -animation
  • Nextbio
The source of this article is wikipedia, the free encyclopedia.  The text of this article is licensed under the GFDL.
 
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