Editing Histone octamer (section)

==The histone octamer in the nucleosome==
{{Further|Nucleosome}}

[[File:Nucleosome structure.png|thumb|alt=Nucleosome assembly|The nucleosome assembles when DNA wraps around the histone octamer, two H2A-H2B dimers bound to an H3-H4 tetramer.]]

The nucleosome core particle is the most basic form of DNA compaction in [[eukaryote]]s. Nucleosomes consist of a histone octamer surrounded by 146 base pairs of DNA wrapped in a [[superhelix|superhelical]] manner.<ref name="andrews">{{cite journal|last=Andrews|first=Andrew J.|author2=Luger, Karolin|title=Nucleosome Structure(s) and Stability: Variations on a Theme|journal=Annual Review of Biophysics|date=9 June 2011|volume=40|issue=1|pages=99–117|doi=10.1146/annurev-biophys-042910-155329|pmid=21332355}}</ref>  In addition to compacting the DNA, the histone octamer plays a key role in the transcription of the DNA surrounding it. The histone octamer interacts with the DNA through both its core histone folds and N-terminal tails. The histone fold interacts chemically and physically with the DNA's [[Minor groove#Grooves|minor groove]]. Studies have found that the histones interact more favorably with [[adenine|A]]:[[thymine|T]] enriched regions than [[guanine|G]]:[[cytosine|C]] enriched regions in the minor grooves.<ref name="watson">{{cite book|last=School|first=James D. Watson, Cold Spring Harbor Laboratory, Tania A. Baker, Massachusetts Institute of Technology, Stephen P. Bell, Massachusetts Institute of Technology, Alexander Gann, Cold Spring Harbor Laboratory, Michael Levine, University of California, Berkeley, Richard Losik, Harvard University; with Stephen C. Harrison, Harvard Medical|title=Molecular biology of the gene|publisher=Benjamin-Cummings Publishing Company|location=Boston|isbn=978-0321762436|page=241|edition=Seventh|year=2014}}</ref> The N-terminal tails do not interact with a specific region of DNA but rather stabilize and guide the DNA wrapped around the octamer. The interactions between the histone octamer and DNA, however, are not permanent. The two can be separated quite easily and often are during [[DNA replication|replication]] and [[Transcription (genetics)|transcription]]. Specific remodeling proteins are constantly altering the chromatin structure by breaking the bonds between the DNA and nucleosome.

===Histone/DNA interactions===

Histones are composed of mostly positively charged amino acid residues such as [[lysine]] and [[arginine]]. The positive charges allow them to closely associate with the negatively charged DNA through electrostatic interactions. Neutralizing the charges in the DNA allows it to become more tightly packed.<ref name=watson />

====Interactions with the minor groove====

The histone-fold domains’ interaction with the minor groove accounts for the majority of the interactions in the nucleosome.<ref name=luger>{{cite journal|last=Richmond|first=Timothy J.|author2=Luger, Karolin |author3=Mäder, Armin W. |author4=Richmond, Robin K. |author5= Sargent, David F. |journal=Nature|date=18 September 1997|volume=389|issue=6648|pages=251–260|doi=10.1038/38444|pmid=9305837 |title=Crystal structure of the nucleosome core particle at 2.8 A resolution|bibcode=1997Natur.389..251L|s2cid=4328827}}</ref> As the DNA wraps around the histone octamer, it exposes its minor groove to the histone octamer at 14 distinct locations. At these sites, the two interact through a series of weak, non-covalent bonds. The main source of bonds comes from hydrogen bonds, both direct and water-mediated.<ref name=andrews /> The histone-fold hydrogen bonds  with both phosphodiester backbone and the A:T rich bases. In these interactions, the histone fold binds to the oxygen atoms and [[hydroxyl]] side chains, respectively.<ref name=luger /> Together these sites have a total of about 40 hydrogen bonds, most of which are from the backbone interactions.<ref name=watson /> Additionally, 10 out of the 14 times that the minor groove faces the histone fold, an arginine side chain from the histone fold is inserted into the minor groove. The other four times, the arginine comes from a tail region of the histone.<ref name=luger />

====Tail interactions and modifications====
{{Further|Histone}}
As mentioned above the histone tails have been shown to directly interact with the DNA of the nucleosome. Each histone in the octamer has an N-terminal tail that protrudes from the histone core. The tails play roles both in inter and intra nucleosomal interactions that ultimately influence gene access.<ref name=biswas>{{cite journal|last=Biswas|first=Mithun|author2=Voltz, Karine |author3=Smith, Jeremy C. |author4= Langowski, Jörg |title=Role of Histone Tails in Structural Stability of the Nucleosome|journal=PLOS Computational Biology|date=15 December 2011|volume=7|issue=12|pages=e1002279|doi=10.1371/journal.pcbi.1002279|pmid=22207822|pmc=3240580|bibcode=2011PLSCB...7E2279B |doi-access=free }}</ref> Histones are positively charged molecules which allow a tighter bonding to the negatively charged DNA molecule. Reducing the positive charge of histone proteins reduces the strength of binding between the histone and DNA, making it more open to gene transcription (expression).<ref name="biswas"/> Moreover, these flexible units direct DNA wrapping in a left-handed manner around the histone octamer during nucleosome formation.<ref name=watson /> Once the DNA is bound the tails continue to interact with the DNA. The parts of the tail closest to the DNA hydrogen bond and strengthen the DNA's association with the octamer; the parts of the tail furthest away from the DNA, however, work in a very different manner. Cellular enzymes modify the amino acids in the distal sections of the tail to influence the accessibility of the DNA. The tails have also been implicated in the stabilization of 30-nm fibers. Research has shown removing certain tails prevents the nucleosomes from forming properly and a general failure to produce chromatin fiber.<ref name=biswas /> In all, these associations protect the nucleosomal DNA from the external environment but also lower their accessibility to cellular replication and transcriptional machinery.

===Nucleosome remodeling and disassembly===
{{Further|Chromatin remodeling}}
In order to access the nucleosomal DNA, the bonds between it and the histone octamer must be broken. This change takes place periodically in the cell as specific regions are transcribed, and it happens genome-wide during replication. Remodeling proteins work in three distinct ways: they can slide the DNA along the surface of the octamer, replace the one histone dimer with a variant, or remove the histone octamer entirely. No matter the method, in order to modify the nucleosomes, the remodeling complexes require energy from ATP hydrolysis to drive their actions.

Of the three techniques, sliding is the most common and least extreme.<ref>{{cite journal|last=Becker|first=P. B.|title=NEW EMBO MEMBER'S REVIEW: Nucleosome sliding: facts and fiction|journal=The EMBO Journal|date=16 September 2002|volume=21|issue=18|pages=4749–4753|doi=10.1093/emboj/cdf486|pmid=12234915|pmc=126283}}</ref>  The basic premise of the technique is to free up a region of DNA that the histone octamer would normally tightly bind. While the technique is not well defined, the most prominent hypothesis is that the sliding is done in an “inchworm” fashion. In this method, using ATP as an energy source, the translocase domain of the nucleosome-remodeling complex detaches a small region of DNA from the histone octamer. This “wave” of DNA, spontaneously breaking and remaking the hydrogen bonds as it goes, then propagates down the nucleosomal DNA until it reaches the last binding site with the histone octamer. Once the wave reaches the end of the histone octamer the excess that was once at the edge is extended into the region of linker DNA. In total, one round of this method moves the histone octamer several base pairs in a particular direction—away from the direction the “wave” propagated.<ref name=watson /><ref>{{cite journal|last=Fazzio|first=TG|author2=Tsukiyama, T|title=Chromatin remodeling in vivo: evidence for a nucleosome sliding mechanism.|journal=Molecular Cell|date=November 2003|volume=12|issue=5|pages=1333–40|pmid=14636590|doi=10.1016/s1097-2765(03)00436-2|doi-access=free}}</ref>