Histone 14029 225757337 2008-07-15T07:15:28Z Rjwilmsi 203434 gen fixes + link/fix date fields in cite templates (explanation [[User:Rjwilmsi#My_correction_of_dates_in_templates|here]]) using [[Project:AutoWikiBrowser|AWB]] [[Image:Nucleosome structure.png|thumb|300px|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]]. Without histones, the unwound DNA in chromosomes would be very long. For example, each human cell has about 1.8 meters of DNA, but wound on the histones it has about 90 millimeters of chromatin, which, when duplicated and condensed during [[mitosis]], result in about 120 micrometers of [[chromosome]]s.<ref> Redona C, Pilcha D, Rogakoub E, Sedelnikovaa O, Newrocka K, Bonnera W. "[http://www.ncbi.nlm.nih.gov/pubmed/11893489?ordinalpos=2&itool=EntrezSystem2.PEntrez.Pubmed.Pubmed_ResultsPanel.Pubmed_RVDocSum Histone H2A variants H2AX and H2AZ]." ''Current Opinion in Genetics & Development'' 2002 Apr 1; 12(2): 162-169. PMID 11893489</ref> ==Classes== Six ''major histone'' classes are known: :* [[Histone H1|H1]] (sometimes called the linker histone; also related to [[Histone H5]].) :* [[Histone H2A|H2A]] :* [[Histone H2B|H2B]] :* [[Histone H3|H3]] :* [[Histone H4|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<ref name="pmid9305837">{{cite journal |author=Luger K, Mäder AW, Richmond RK, Sargent DF, Richmond TJ |title=Crystal structure of the nucleosome core particle at 2.8 A resolution |journal=Nature |volume=389 |issue=6648 |pages=251–60 |year=1997 |pmid=9305837 |doi=10.1038/38444}}[http://www.pdb.org/pdb/explore.do?structureId=1AOI PDB entry 1AOI]</ref>. The linker histone H1 binds the nucleosome and the entry and exit sites of the DNA, thus locking the DNA into place <ref>(Daniel H. Farkas. Histone.In: DNA Simplified. THe Hitchhiker's Guide to DNA. AACC Press .Washington, D.C.) 0-915274-84-1</ref> 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 [[chromosome]]s are assembled through interactions between nucleosomes and other regulatory proteins. ==Structure== The [[nucleosome]] core is formed of two H2A-H2B [[dimers]] and a H3-H4 tetramer, forming two nearly [[symmetry|symmetrical]] halves by [[tertiary structure]] ([[Point groups in three dimensions|C2]] symmetry; one [[macromolecule]] is the mirror image of the other)<ref name="pmid9305837"/>. 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). In all, histones make five types of interactions with DNA: # Helix-dipoles from [[alpha helix|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. # [[Hydrogen bonds]] between the DNA backbone and the [[Amide#Amide_linkage_.28peptide_bond.29|amide]] group on the main chain of histone proteins. # Nonpolar interactions between the histone and [[deoxyribose]] sugars on DNA. # Salt links and hydrogen bonds between side chains of basic amino acids (especially [[lysine]] and [[arginine]]) 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 the water solubility of histones.{{fact|date=July 2007}} Histones are subject to posttranslational modification by enzymes primarily on their N-terminal tails, but also in their globular domains{{fact|date=July 2007}}. Such modifications include [[methylation]], [[citrullination]], [[acetylation]], [[phosphorylation]], [[Sumoylation]], [[ubiquitin]]ation, and [[ADP-ribosylation]]. This affects their function of gene regulation (see functions). In general, [[gene]]s that are active have less bound histone, while inactive genes are highly associated with histones during [[interphase]]{{fact|date=July 2007}}. It also appears that the structure of histones has been [[evolution]]arily conserved, as any deleterious [[mutations]] would be severely maladaptive. ==Functions== ===Compacting DNA Strands=== Histones act as spools around which DNA winds. This enables the compaction necessary to fit the large [[genome]]s of eukaryotes inside cell nuclei: the compacted molecule is 30,000 times shorter than an unpacked molecule. ===Histone modifications in [[chromatin]] regulation=== Histones undergo [[posttranslational modification]]s which alter their interaction with [[DNA]] and nuclear proteins. The H3 and H4 histones have long tails protruding from the nucleosome which can be [[covalent]]ly 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]]"<ref name="pmid10638745">{{cite journal |author=Strahl BD, Allis CD |title=The language of covalent histone modifications |journal=Nature |volume=403 |issue=6765 |pages=41–5 |date=[[6 January]] [[2000]] |pmid=10638745 |doi=10.1038/47412}}</ref><ref name="pmid11498575">{{cite journal |author=Jenuwein T, Allis CD |title=Translating the histone code |journal=Science |volume=293 |issue=5532 |pages=1074–80 |date=[[10 August]] [[2001]] |pmid=11498575 |doi=10.1126/science.1063127}}</ref>. Histone modifications act in diverse biological processes such as [[gene regulation]], [[DNA repair]] and chromosome condensation ([[mitosis]]).{{fact|date=July 2007}} The common nomenclature of histone modifications is as follows: #The name of the histone (''e.g'' H3) #The single letter [[amino acid]] abbreviation (''e.g.'' K for [[Lysine]]) and the amino acid position in the protein #The type of modification (Me: [[methyl]], P: [[phosphate]], Ac: [[acetyl]], Ub: [[ubiquitin]]) So H3K4me1 denotes the monomethylation of H3 on the 4th lysine from the start ([[N-terminal]]) of the protein. For a detailed example of histone modifications in [[transcription (genetics)|transcription]] regulation see [[RNA polymerase control by chromatin structure]] and table. ====Influence on gene expression in mammalian cells:==== {| class="wikitable" |- ! Type of modification |- ! <ref name="a">{{cite journal |author=Barski A, Cuddapah S, Cui K, ''et al'' |title=High-resolution profiling of histone methylations in the human genome |journal=Cell |volume=129 |issue=4 |pages=823–37 |year=2007 |pmid=17512414 |doi=10.1016/j.cell.2007.05.009}}</ref><ref name="b">{{cite journal |author=Benevolenskaya EV |title=Histone H3K4 demethylases are essential in development and differentiation |journal=Biochem. Cell Biol. |volume=85 |issue=4 |pages=435–43 |year=2007 |pmid=17713579 |doi=10.1139/o07-057}}</ref><ref name="c">{{cite journal |author=Steger DJ, Lefterova MI, Ying L, ''et al'' |title=DOT1L/KMT4 recruitment and H3K79 methylation are ubiquitously coupled with gene transcription in mammalian cells |journal=Mol. Cell. Biol. |volume=28 |issue=8 |pages=2825–39 |year=2008 |pmid=18285465 |doi=10.1128/MCB.02076-07}}</ref><ref name="d">{{cite journal |author=Koch CM, Andrews RM, Flicek P, ''et al'' |title=The landscape of histone modifications across 1% of the human genome in five human cell lines |journal=Genome Res. |volume=17 |issue=6 |pages=691–707 |year=2007 |pmid=17567990 |doi=10.1101/gr.5704207}}</ref> ! H3K4 ! H3K9 ! H3K27 ! H3K79 ! H4K20 ! H2BK5 |- | mono[[methylation]] | [[gene activation|activation]]<ref name="b"/> | [[gene activation|activation]]<ref name="a"/> | [[gene activation|activation]]<ref name="a"/> | [[gene activation|activation]]<ref name="a"/><ref name="c"/> | [[gene activation|activation]]<ref name="a"/> | [[gene activation|activation]]<ref name="a"/> |- | di[[methylation]] | | | | [[gene activation|activation]]<ref name="c"/> | | |- | tri[[methylation]]s | [[gene activation|activation]]<ref name="d"/> | [[gene repression|repression]]<ref name="a"/> | [[gene repression|repression]]<ref name="a"/> | [[gene repression|repression]]<ref name="a"/>[[gene activation|activation]]<ref name="c"/> | | |- ! ! H3K9 ! H3K14 ! ! ! ! |- | [[acetylation]] | [[gene activation|activation]]<ref name="d"/> | [[gene activation|activation]]<ref name="d"/> | | | | |} ==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{{fact|date=July 2007}}. ==Conservation across species== Histones are found in the [[nucleus (biology)|nuclei]] of [[eukaryote|eukaryotic]] [[cell (biology)|cells]], and in certain [[Archaea]], namely [[Euryarchaeota|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.{{fact|date=July 2007}} 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.{{fact|date=July 2007}} 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 break]]s and marks the region undergoing [[DNA repair]]. Histone H3.3 is associated with the body of actively transcribed genes.{{fact|date=July 2007}} ==See also== * [[Nucleosome]] * [[Chromatin]] * [[Histone-Modifying Enzymes]] * [[Histone deacetylase]] * [[PRMT4 pathway]] * [[Gene silencing]] * [[Genetics]] * [[Histone methyltransferase]] * [[Histone acetyltransferase]] ==References== {{reflist}} {{Chromo}} [[Category:Epigenetics]] [[Category:Genetics]] [[Category:Proteins]] [[ar:هيستون]] [[ca:Histona]] [[cs:Histon]] [[da:Histon]] [[de:Histon]] [[es:Histona]] [[fa:هیستون]] [[fr:Histone]] [[ko:히스톤]] [[it:Istone]] [[he:היסטון]] [[lt:Histonas]] [[hu:Hiszton]] [[nl:Histon (eiwit)]] [[ja:ヒストン]] [[oc:Istòna]] [[pl:Histony]] [[pt:Histona]] [[ru:Гистоны]] [[sl:Histon]] [[sr:Хистони]] [[fi:Histoni]] [[sv:Histon]] [[tr:Histon]] [[uk:Гістони]] [[zh:組織蛋白]]