Editing Nucleosome (section)

{{Short description|Basic structural unit of DNA packaging in eukaryotes}}
[[File:Basic units of chromatin structure.svg|thumb|Basic units of [[chromatin]] structure]]

A '''nucleosome''' is the basic structural unit of [[DNA]] packaging in [[eukaryotes]]. The structure of a nucleosome consists of a segment of DNA wound around eight [[histone|histone proteins]]<ref name="Campbell">{{cite book | vauthors = Reece J, Campbell N | title = Biology | publisher = Benjamin Cummings | location = San Francisco | year = 2006 | isbn = 978-0-8053-6624-2 | url-access = registration | url = https://archive.org/details/biologyc00camp }}</ref> and resembles thread wrapped around a [[bobbin|spool]]. The nucleosome is the fundamental subunit of [[chromatin]]. Each nucleosome is composed of a little less than two turns of DNA wrapped around a set of eight proteins called histones, which are known as a [[histone octamer]]. Each histone octamer is composed of two copies each of the histone proteins [[Histone H2A|H2A]], [[Histone H2B|H2B]], [[Histone H3|H3]], and [[Histone H4|H4]].

DNA must be compacted into nucleosomes to fit within the [[cell nucleus]].<ref name="AlbertMBOCp207">{{cite book | vauthors = Alberts B |title=Molecular biology of the cell |chapter=Chromosomal DNA and Its Packaging in the Chromatin Fiber |publisher=Garland Science |location=New York |year=2002 |page=207 |isbn=978-0-8153-4072-0 |edition=4th |url=https://www.ncbi.nlm.nih.gov/books/bv.fcgi?highlight=Nucleosome&rid=mboc4.section.608#630}}</ref> In addition to nucleosome wrapping, eukaryotic [[chromatin]] is further compacted by being folded into a series of more complex structures, eventually forming a [[chromosome]]. Each human cell contains about 30 million nucleosomes.<ref name="howmany">{{cite book |title=Chromosomal DNA and Its Packaging in the Chromatin Fiber |year = 2002 |url= https://www.ncbi.nlm.nih.gov/books/NBK26834/#:~:text=On%20average%2C%20therefore%2C%20nucleosomes%20repeat,contains%20approximately%2030%20million%20nucleosomes | vauthors = lberts B, Johnson A, Lewis J, Raff M, Roberts K, Walter P  |publisher = Garland Science }}</ref>

Nucleosomes are thought to carry [[Epigenetics|epigenetically]] inherited information in the form of [[covalent modification]]s of their core [[histones]]. Nucleosome positions in the genome are not random, and it is important to know where each nucleosome is located because this determines the accessibility of the DNA to [[regulatory protein]]s.<ref>{{cite journal | vauthors = Teif VB, Clarkson CT | title = Nucleosome Positioning | journal = Encyclopedia of Bioinformatics and Computational Biology | volume = 2| pages = 308–317 | date = 2019 | doi = 10.1016/B978-0-12-809633-8.20242-2 | isbn = 9780128114322 | s2cid = 43929234 }}</ref>

Nucleosomes were first observed as particles in the electron microscope by Don and Ada Olins in 1974,<ref>{{cite journal | vauthors = Olins AL, Olins DE | title = Spheroid chromatin units (v bodies) | journal = Science | volume = 183 | issue = 4122 | pages = 330–332 | date = January 1974 | pmid = 4128918 | doi = 10.1126/science.183.4122.330 | s2cid = 83480762 | bibcode = 1974Sci...183..330O }}</ref> and their existence and structure (as histone octamers surrounded by approximately 200 base pairs of DNA) were proposed by [[Roger Kornberg]].<ref>{{cite journal | vauthors = McDonald D | title = Milestone 9, (1973-1974) The nucleosome hypothesis: An alternative string theory | journal = Nature Milestones: Gene Expression. | date = December 2005 | url = http://www.nature.com/milestones/geneexpression/milestones/articles/milegene09.html | doi=10.1038/nrm1798| url-access = subscription }}</ref><ref>{{cite journal | vauthors = Kornberg RD | title = Chromatin structure: a repeating unit of histones and DNA | journal = Science | volume = 184 | issue = 4139 | pages = 868–871 | date = May 1974 | pmid = 4825889 | doi = 10.1126/science.184.4139.868 | bibcode = 1974Sci...184..868K }}</ref> The role of the nucleosome as a regulator of transcription was demonstrated by Lorch et al. in vitro<ref>{{cite journal | vauthors = Lorch Y, LaPointe JW, Kornberg RD | title = Nucleosomes inhibit the initiation of transcription but allow chain elongation with the displacement of histones | journal = Cell | volume = 49 | issue = 2 | pages = 203–210 | date = April 1987 | pmid = 3568125 | doi = 10.1016/0092-8674(87)90561-7 | s2cid = 21270171 | doi-access = free }}</ref> in 1987 and by Han and Grunstein<ref>{{cite journal | vauthors = Han M, Grunstein M | title = Nucleosome loss activates yeast downstream promoters in vivo | journal = Cell | volume = 55 | issue = 6 | pages = 1137–1145 | date = December 1988 | pmid = 2849508 | doi = 10.1016/0092-8674(88)90258-9 | s2cid = 41520634 }}</ref> and Clark-Adams et al.<ref>{{cite journal | vauthors = Clark-Adams CD, Norris D, Osley MA, Fassler JS, Winston F | title = Changes in histone gene dosage alter transcription in yeast | journal = Genes & Development | volume = 2 | issue = 2 | pages = 150–159 | date = February 1988 | pmid = 2834270 | doi = 10.1101/gad.2.2.150 | doi-access = free }}</ref> in vivo in 1988.

The nucleosome core particle consists of approximately 146 [[base pair]]s (bp) of [[DNA]]<ref name="diffbp">In different crystals, values of 146 and 147 basepairs were observed</ref> wrapped in 1.67 left-handed [[Supercoil|superhelical turns]] around a [[histone]] octamer, consisting of 2 copies each of the core histones [[Histone H2A|H2A]], [[Histone H2B|H2B]], [[Histone H3|H3]], and [[Histone H4|H4]].<ref name="autogenerated1">{{cite journal | vauthors = 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 = 251–260 | date = September 1997 | pmid = 9305837 | doi = 10.1038/38444 | s2cid = 4328827 | bibcode = 1997Natur.389..251L }}</ref> Core particles are connected by stretches of [[linker DNA]], which can be up to about 80 bp long. Technically, a nucleosome is defined as the core particle plus one of these linker regions; however the word is often synonymous with the core particle.<ref name="Alberts5edp211">{{cite book | vauthors = Alberts B |title=Molecular Biology of the Cell |publisher=Garland Science |location=New York |year=2007 |page=211 |isbn=978-0-8153-4106-2 |edition=5th}}</ref> Genome-wide nucleosome positioning maps are now available for many model organisms and human cells.<ref>{{cite journal | vauthors = Shtumpf M, Piroeva KV, Agrawal SP, Jacob DR, Teif VB | title = NucPosDB: a database of nucleosome positioning in vivo and nucleosomics of cell-free DNA | journal = Chromosoma | volume = 131 | issue = 1–2 | pages = 19–28 | date = June 2022 | pmid = 35061087 | pmc = 8776978 | doi = 10.1007/s00412-021-00766-9 }}</ref>

Linker histones such as [[Histone H1|H1]] and its isoforms are involved in chromatin compaction and sit at the base of the nucleosome near the DNA entry and exit binding to the linker region of the DNA.<ref>{{cite journal | vauthors = Zhou YB, Gerchman SE, Ramakrishnan V, Travers A, Muyldermans S | title = Position and orientation of the globular domain of linker histone H5 on the nucleosome | journal = Nature | volume = 395 | issue = 6700 | pages = 402–405 | date = September 1998 | pmid = 9759733 | doi = 10.1038/26521 | s2cid = 204997317 | bibcode = 1998Natur.395..402Z | doi-access = free }}</ref> Non-condensed nucleosomes without the linker histone resemble "beads on a string of DNA" under an [[electron microscope]].<ref>{{cite journal | vauthors = Thoma F, Koller T, Klug A | title = Involvement of histone H1 in the organization of the nucleosome and of the salt-dependent superstructures of chromatin | journal = The Journal of Cell Biology | volume = 83 | issue = 2 Pt 1 | pages = 403–427 | date = November 1979 | pmid = 387806 | pmc = 2111545 | doi = 10.1083/jcb.83.2.403 }}</ref>

In contrast to most eukaryotic cells, mature sperm cells largely use [[protamines]] to package their genomic DNA, most likely to achieve an even higher packaging ratio.<ref name="pmid1297351">{{cite journal | vauthors = Clarke HJ | title = Nuclear and chromatin composition of mammalian gametes and early embryos | journal = Biochemistry and Cell Biology | volume = 70 | issue = 10–11 | pages = 856–866 | year = 1992 | pmid = 1297351 | doi = 10.1139/o92-134 }}</ref> Histone equivalents and a simplified chromatin structure have also been found in [[Archaea]],<ref name="pmid12540921">{{cite journal | vauthors = Felsenfeld G, Groudine M | title = Controlling the double helix | journal = Nature | volume = 421 | issue = 6921 | pages = 448–453 | date = January 2003 | pmid = 12540921 | doi = 10.1038/nature01411 | doi-access = free | bibcode = 2003Natur.421..448F }}</ref> suggesting that eukaryotes are not the only organisms that use nucleosomes.