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

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. Image File history File links Question_book-3. ... Image File history File links Download high resolution version (1024x610, 232 KB) Summary By Richard Wheeler (Zephyris) 2005; Schematic representation of the assembly of the core histones into the nucleosome. ... Image File history File links Download high resolution version (1024x610, 232 KB) Summary By Richard Wheeler (Zephyris) 2005; Schematic representation of the assembly of the core histones into the nucleosome. ... For the song by Girls Aloud see Biology (song) Biology studies the variety of life (clockwise from top-left) E. coli, tree fern, gazelle, Goliath beetle Biology (from Greek: βίος, bio, life; and λόγος, logos, speech lit. ... A representation of the 3D structure of myoglobin, showing coloured alpha helices. ... Chromatin is the complex of DNA and protein found inside the nuclei of eukaryotic cells. ... The structure of part of a DNA double helix Deoxyribonucleic acid, or DNA, is a nucleic acid molecule that contains the genetic instructions used in the development and functioning of all known living organisms. ... Gene regulation is the general term for cellular control of protein synthesis at the DNA-RNA transcription step. ...

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^[1]. The linker histone H1 binds the nucleosome and the entry and exit sites of the DNA, thus locking the DNA into place^{[citation needed]} 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. Histone H1 is one of the 5 main histone proteins involved in the structure of chromatin in eukaryotic cells. ... Histone H1 is one of the 5 main histone proteins involved in the structure of chromatin in eukaryotic cells. ... Histone H2A is one of the 5 main histone proteins involved in the structure of chromatin in eukaryotic cells. ... Histone H2B is one of the 5 main histone proteins involved in the structure of chromatin in eukaryotic cells. ... H3 (Histone H3) is one of the 5 main histone proteins involved in the structure of chromatin in eukaryotic cells. ... H4 (Histone H4) is one of the 5 main histone proteins involved in the structure of chromatin in eukaryotic cells. ... A nucleosome is a unit made of DNA and histones. ... In genetics, two nucleotides on opposite complementary DNA or RNA strands that are connected via hydrogen bonds are called a base pair (often abbreviated bp). ... The structure of part of a DNA double helix Deoxyribonucleic acid, or DNA, is a nucleic acid molecule that contains the genetic instructions used in the development and functioning of all known living organisms. ... A nucleosome is a unit made of DNA and histones. ... The structure of part of a DNA double helix Deoxyribonucleic acid, or DNA, is a nucleic acid molecule that contains the genetic instructions used in the development and functioning of all known living organisms. ... The structure of part of a DNA double helix Deoxyribonucleic acid, or DNA, is a nucleic acid molecule that contains the genetic instructions used in the development and functioning of all known living organisms. ... Chromatin is the complex of DNA and protein found inside the nuclei of eukaryotic cells. ... A scheme of a condensed (metaphase) chromosome. ...

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)^[1]. 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, 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). A nucleosome is a unit made of DNA and histones. ... Sucrose, or common table sugar, is composed of glucose and fructose. ... Sphere symmetry group o. ... In biochemistry and chemistry, the tertiary structure of a protein or any other macromolecule is its three-dimensional structure, as defined by the atomic coordinates. ... A discrete point group in 3D is a finite symmetry group in 3D that leaves the origin fixed. ... Illustration of a polypeptide macromolecule The term macromolecule by definition implies large molecule. In the context of biochemistry, the term may be applied to the four conventional biopolymers (nucleotides, proteins, carbohydrates, and lipids), as well as non-polymeric molecules with large molecular mass such as macrocycles. ... This article is about evolution in biology. ... This article is about the class of chemicals. ...

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.^{[citation needed]} Side view of an α-helix of alanine residues in atomic detail. ... A phosphate, in inorganic chemistry, is a salt of phosphoric acid. ... In chemistry, a hydrogen bond is a type of attractive intermolecular force that exists between two partial electric charges of opposite polarity. ... Deoxyribose Deoxyribose, also known as D-Deoxyribose and 2-deoxyribose, is an aldopentose — a monosaccharide containing five carbon atoms, and including an aldehyde functional group. ... Lysine is one of the 20 amino acids normally found in proteins. ... Arginine (abbreviated as Arg or R)[1] is an α-amino acid. ...

Histones are subject to posttranslational modification by enzymes primarily on their N-terminal tails, but also in their globular domains^{[citation needed]}. Such modifications include methylation, citrullination, acetylation, phosphorylation, Sumoylation, ubiquitination, and ADP-ribosylation. This affects their function of gene regulation (see functions). Methylation is a term used in the chemical sciences to denote the attachment or substitution of a methyl group on various substrates. ... 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. ... Acetylation describes a reaction, usually with acetic acid, that introduces an acetyl functional group into an organic compound. ... A phosphorylated serine residue Phosphorylation is the addition of a phosphate (PO4) group to a protein molecule or a small molecule. ... Ubiquitin is a very conserved small regulatory protein that is ubiquitous in eukaryotes. ... ADP ribose ADP-ribosylation is a posttranslational modification of proteins that involves the addition of one or more ADP and ribose moieties. ...

In general, genes that are active have less bound histone, while inactive genes are highly associated with histones during interphase^{[citation needed]}. It also appears that the structure of histones have been evolutionarily conserved, as any deleterious mutations would be severely maladaptive. For other uses, see Gene (disambiguation). ... Interphase is a phase of the cell cycle. ... This article is about evolution in biology. ... This article is about mutation in biology, for other meanings see: mutation (disambiguation). ...

Functions

Compacting DNA Strands

Histones act as spools around which DNA winds. This enables the compaction necessary to fit the large genomes of eukaryotes inside cell nuclei: the compacted molecule is 50,000 times shorter than an unpacked molecule.^{[citation needed]} In biology the genome of an organism is the whole hereditary information of an organism that is encoded in the DNA (or, for some viruses, RNA). ...

Histone modifications 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, phosphorylation, ubiquitination, sumoylation, citrullination, and ADP-ribosylation. 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"^[2][3]. Histone modifications act in diverse biological processes such as gene regulation, DNA repair and chromosome condensation (mitosis).^{[citation needed]} Chromatin is the complex of DNA and protein found inside the nuclei of eukaryotic cells. ... Posttranslational modification is the chemical modification of a protein after its translation. ... The structure of part of a DNA double helix Deoxyribonucleic acid, or DNA, is a nucleic acid molecule that contains the genetic instructions used in the development and functioning of all known living organisms. ... Covalent bonding is a form of chemical bonding characterized by the sharing of one or more pairs of electrons between atoms, in order to produce a mutual attraction, which holds the resultant molecule together. ... Methylation is a term used in the chemical sciences to denote the attachment or substitution of a methyl group on various substrates. ... Acetylation describes a reaction, usually with acetic acid, that introduces an acetyl functional group into an organic compound. ... A phosphorylated serine residue Phosphorylation is the addition of a phosphate (PO4) group to a protein molecule or a small molecule. ... // Background Ubiquitylation, also termed ubiquitination, refers to the process particular to eukaryotes whereby a protein is post-translationally modified by covalent attachment of a small protein. ... Small Ubiquitin-related 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. ... 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. ... ADP ribose ADP-ribosylation is a posttranslational modification of proteins that involves the addition of one or more ADP and ribose moieties. ... The Histone Code is hypothesized to be a code consisting of covalent histone tail modifications. ... Gene regulation is the general term for cellular control of protein synthesis at the DNA-RNA transcription step. ... DNA damage resulting in multiple broken chromosomes DNA repair refers to a collection of processes by which a cell identifies and corrects damage to the DNA molecules that encode its genome. ... Mitosis divides genetic information during cell division. ...

The common nomenclature 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. This article is about the class of chemicals. ... Lysine is one of the 20 amino acids normally found in proteins. ... In chemistry a methyl-group is a hydrophobic Alkyl functional group which is derived from methane (CH4). ... A phosphate, in inorganic chemistry, is a salt of phosphoric acid. ... Acetyl is the radical of acetic acid. ... Ubiquitin is a very conserved small regulatory protein that is ubiquitous in eukaryotes. ... The N-terminal end refers to the extremity of a protein or polypeptide terminated by an amino acid with a free amine group (NH2). ...

For a detailed example of histone modifications in transcription regulation see RNA polymerase control by chromatin structure. A micrograph of ongoing gene transcription of ribosomal RNA illustrating the growing primary transcripts. ... This is an outline of an example mechanism of yeast cells by which chromatin structure and histone posttranslational modification help regulate and record the transcription of genes by RNA polymerase II. This pathway gives examples of regulation at these points of transcription: Pre-initiation (promotion by Bre1, histone modification) Initiation...

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^{[citation needed]}. Ludwig Karl Martin Leonhard Albrecht Kossel (September 16, 1853 - July 5, German medical doctor. ... Alternative meaning: Nineteenth Century (periodical) (18th century — 19th century — 20th century — more centuries) As a means of recording the passage of time, the 19th century was that century which lasted from 1801-1900 in the sense of the Gregorian calendar. ...

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.^{[citation needed]} There are two meanings of the word nucleus in biology: The cell nucleus is an organelle within an eukaryotic cell. ... Kingdoms Animalia - Animals Fungi Plantae - Plants Chromalveolata Protista Alternative phylogeny Unikonta Opisthokonta Metazoa Choanozoa Eumycota Amoebozoa Bikonta Apusozoa Cabozoa Rhizaria Excavata Corticata Archaeplastida Chromalveolata Animals, plants, fungi, and protists are eukaryotes (IPA: ), organisms whose cells are organized into complex structures by internal membranes and a cytoskeleton. ... Drawing of the structure of cork as it appeared under the microscope to Robert Hooke from Micrographia which is the origin of the word cell being used to describe the smallest unit of a living organism Cells in culture, stained for keratin (red) and DNA (green) The cell is the... Phyla Crenarchaeota Euryarchaeota Korarchaeota Nanoarchaeota ARMAN The Archaea (), or archaebacteria, are a major group of microorganisms. ... Classes Archaeoglobi Halobacteria Methanobacteria Methanococci Methanomicrobia Methanopyri Thermococci Thermoplasmata The Euryarchaeota are a major group of Archaea. ... Phyla Actinobacteria Aquificae Chlamydiae Bacteroidetes/Chlorobi Chloroflexi Chrysiogenetes Cyanobacteria Deferribacteres Deinococcus-Thermus Dictyoglomi Fibrobacteres/Acidobacteria Firmicutes Fusobacteria Gemmatimonadetes Lentisphaerae Nitrospirae Planctomycetes Proteobacteria Spirochaetes Thermodesulfobacteria Thermomicrobia Thermotogae Verrucomicrobia Bacteria (singular: bacterium) are unicellular microorganisms. ...

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.^{[citation needed]}

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 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.^{[citation needed]} Chromosome. ... For differently-colored eyes, see Heterochromia. ... DNA damage resulting in multiple broken chromosomes DNA repair refers to a collection of processes by which a cell identifies and corrects damage to the DNA molecules that encode its genome. ...

See also

• Nucleosome
• Chromatin
• Histone-Modifying Enzymes
• Histone deacetylase
• PRMT4 pathway
• Gene silencing
• Genetics
• Histone methyltransferase
• Histone acetyltransferase

A nucleosome is a unit made of DNA and histones. ... Chromatin is the complex of DNA and protein found inside the nuclei of eukaryotic cells. ... Histone-Modifying Enzymes, the sites for modification are marked in color. ... Histone deacetylases (HDAC) are a class of enzymes that remove acetyl groups from an ε-N-acetyl lysine amino acid on a histone. ... PRMT4 pathway Protein arginine N-methyltransferase-4 (PRMT4/CARM1)[1][2][3] methylation of arginine residues within proteins plays a critical key role in transcriptional regulation (see the PRMT4 pathway on the left). ... Gene silencing is a general term describing epigenetic processes of gene regulation. ... This article is about the general scientific term. ... Histone methyltransferases (HMT) are enzymes which catalyze the transfer of one to three methyl groups from the cofactor s-adenosylmethionine to lysine and arginine residues of histone proteins. ... Histone acetyltransferase (HAT) are enzymes that acetylate conserved lysine amino acids on histone proteins by transferring an acetyl group from acetyl CoA to lysine to form ε-N-acetyl lysine. ...

References