Histone - AbsoluteAstronomy.com

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...

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

separating each pair of nucleosome

Nucleosome

s (also referred to as linker DNA

DNA

). The assembled histones and DNA

DNA

is called chromatin

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 chromosome

Chromosome

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

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

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

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

, 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

, 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

) 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
Type of modification	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 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

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

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

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.

Classes

Structure

Compacting DNA strands

Chromatin regulation

History

Conservation across species

See also

External links