Histone

Assembly of histones into a nucleosome

Histones are proteins found in eukaryotic cell nuclei, which package the DNA into structural units called nucleosomes.<ref name="Youngson">Robert M.,

 Collins dictionary of human biology, 
  
 Glasgow:HarperCollins, 
 2006, 
  
  
 ISBN 0-00-722134-7,</ref><ref name="Nelson&Cox">{{{last}}}, 
 Cox, Michael; Nelson, David R.; Lehninger, Albert L, 
  
 Lehninger principles of biochemistry, 
  
 San Francisco:W.H. Freeman, 
 2005, 
  
  
 ISBN 0-7167-4339-6,</ref> They are the chief protein components of chromatin, the active component of chromosomes. 

Histones act as spools around which DNA winds, and 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 chromosomes.<ref name="pmid11893489">Redon C, Pilch D, Rogakou E, Sedelnikova O, Newrock K, Bonner W,

 Histone H2A variants H2AX and H2AZ, 
 Curr. Opin. Genet. Dev., 
 
 Vol. 12(Issue: 2),
 pp. 162–9,
 DOI: 10.1016/S0959-437X(02)00282-4,
 PMID: 11893489,</ref>

Functions

Compacting DNA strands

Histones act as spools around which DNA winds. This packs in the large genomes of eukaryotes to fit inside cell nuclei. The compacted molecule is 40,000 times shorter than an unpacked molecule.

Chromatin regulation

DNA on outside winding round histone on inside. View from top through helical axis

Histones undergo changes which alter their interaction with DNA and nuclear proteins. Long-term changes in histone/DNA interaction cause epigenetic effects. Combinations of modifications are thought to constitute a code, the so-called histone code.<ref name=pmid10638745>Strahl BD, Allis CD,

 The language of covalent histone modifications, 
 Nature, 
 
 Vol. 403(Issue: 6765),
 pp. 41–5,
 DOI: 10.1038/47412,
 PMID: 10638745,</ref><ref name=pmid11498575>Jenuwein T, Allis CD, 
 Translating the histone code, 
 Science, 
 
 Vol. 293(Issue: 5532),
 pp. 1074–80,
 DOI: 10.1126/science.1063127,
 PMID: 11498575,</ref> Histone modifications act in diverse biological processes such as gene regulation, DNA repair and chromosome condensation (mitosis).

Examples

Examples of histone modifications in transcription regulation include:

Type of modification	Histone
	H3K4	H3K9	H3K14	H3K27	H3K79	H4K20	H2BK5
mono-methylation	activation<ref name="Benevolenskaya_2007">Benevolenskaya EV, Histone H3K4 demethylases are essential in development and differentiation, Biochem. Cell Biol., Vol. 85(Issue: 4), pp. 435–43, DOI: 10.1139/o07-057, PMID: 17713579,</ref>	activation<ref name="Barski_2007">Barski A, Cuddapah S, Cui K, Roh TY, Schones DE, Wang Z, Wei G, Chepelev I, Zhao K, High-resolution profiling of histone methylations in the human genome, Cell, Vol. 129(Issue: 4), pp. 823–37, DOI: 10.1016/j.cell.2007.05.009, PMID: 17512414,</ref>		activation<ref name="Barski_2007"/>	activation<ref name="Barski_2007"/><ref name="Steger_2008">Steger DJ, Lefterova MI, Ying L, Stonestrom AJ, Schupp M, Zhuo D, Vakoc AL, Kim JE, Chen J, Lazar MA, Blobel GA, Vakoc CR, DOT1L/KMT4 recruitment and H3K79 methylation are ubiquitously coupled with gene transcription in mammalian cells, Mol. Cell. Biol., Vol. 28(Issue: 8), pp. 2825–39, DOI: 10.1128/MCB.02076-07, PMID: 18285465, PMC: 2293113,</ref>	activation<ref name="Barski_2007"/>	activation<ref name="Barski_2007"/>
di-methylation		repression<ref name="Rosenfeld_2009">Rosenfeld JA, Wang Z, Schones DE, Zhao K, DeSalle R, Zhang MQ, Determination of enriched histone modifications in non-genic portions of the human genome, BMC Genomics, 2009, Vol. 10, pp. 143, DOI: 10.1186/1471-2164-10-143, PMID: 19335899, PMC: 2667539,</ref>		repression<ref name = "Rosenfeld_2009"/>	activation<ref name="Steger_2008"/>
tri-methylation	activation<ref name="Koch_2007">Koch CM, Andrews RM, Flicek P, Dillon SC, Karaöz U, Clelland GK, Wilcox S, Beare DM, Fowler JC, Couttet P, James KD, Lefebvre GC, Bruce AW, Dovey OM, Ellis PD, Dhami P, Langford CF, Weng Z, Birney E, Carter NP, Vetrie D, Dunham I, The landscape of histone modifications across 1% of the human genome in five human cell lines, Genome Res., Vol. 17(Issue: 6), pp. 691–707, DOI: 10.1101/gr.5704207, PMID: 17567990, PMC: 1891331,</ref>	repression<ref name="Barski_2007"/>		repression<ref name="Barski_2007"/>	activation,<ref name="Steger_2008"/> repression<ref name="Barski_2007"/>		repression<ref name="Rosenfeld_2009"/>
acetylation		activation<ref name="Koch_2007"/>	activation<ref name="Koch_2007"/>

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.<ref name=pmid2171779>Hulton CS, Seirafi A, Hinton JC, Sidebotham JM, Waddell L, Pavitt GD, Owen-Hughes T, Spassky A, Buc H, Higgins CF,

 Histone-like protein H1 (H-NS), DNA supercoiling, and gene expression in bacteria, 
 Cell, 
 
 Vol. 63(Issue: 3),
 pp. 631–42,
 DOI: 10.1016/0092-8674(90)90458-Q,
 PMID: 2171779,</ref>

The discovery of the H5 histone appears to date back to 1970's.<ref name="pmid964248">Crane-Robinson C, Dancy SE, Bradbury EM, Garel A, Kovacs AM, Champagne M, Daune M,

 Structural studies of chicken erythrocyte histone H5, 
 Eur. J. Biochem., 
 
 Vol. 67(Issue: 2),
 pp. 379–88,
 DOI: 10.1111/j.1432-1033.1976.tb10702.x,
 PMID: 964248,</ref><ref name="pmid689022">Aviles FJ, Chapman GE, Kneale GG, Crane-Robinson C, Bradbury EM, 
 The conformation of histone H5. Isolation and characterisation of the globular segment, 
 Eur. J. Biochem., 
 
 Vol. 88(Issue: 2),
 pp. 363–71,
 DOI: 10.1111/j.1432-1033.1978.tb12457.x,
 PMID: 689022,</ref>

Conservation across species

Histones are found in the nuclei of eukaryotic cells, and in certain Archaea, namely Euryarchaea, but not in bacteria. Histone proteins are among the most highly conserved proteins in eukaryotes,<ref>Means: few or no changes between species</ref> which suggests they are vital to the biology of the nucleus.<ref name="Nelson&Cox"/> In contrast, mature sperm cells largely use protamines to package their genomic DNA, most likely to achieve an even higher packaging ratio.<ref name="pmid1297351">Clarke HJ,

 Nuclear and chromatin composition of mammalian gametes and early embryos, 
 Biochem. Cell Biol., 
 1992,
 Vol. 70(Issue: 10-11),
 pp. 856–66,
 DOI: 10.1139/o92-134,
 PMID: 1297351,</ref>

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.