Editing Nucleosome (section)

==Dynamics==
Although the nucleosome is a very stable protein-DNA complex, it is not static and has been shown to undergo a number of different structural re-arrangements including nucleosome sliding and DNA site exposure. Depending on the context, nucleosomes can inhibit or facilitate transcription factor binding. Nucleosome positions are controlled by three major contributions: First, the intrinsic binding affinity of the histone octamer depends on the DNA sequence. Second, the nucleosome can be displaced or recruited by the competitive or [[cooperative binding]] of other protein factors. Third, the nucleosome may be actively translocated by ATP-dependent remodeling complexes.<ref>{{cite journal | vauthors = Teif VB, Rippe K | title = Predicting nucleosome positions on the DNA: combining intrinsic sequence preferences and remodeler activities | journal = Nucleic Acids Research | volume = 37 | issue = 17 | pages = 5641–5655 | date = September 2009 | pmid = 19625488 | pmc = 2761276 | doi = 10.1093/nar/gkp610 }}</ref>

===Nucleosome sliding===
When incubated thermally, nucleosomes reconstituted onto the 5S DNA positioning sequence were able to reposition themselves translationally onto adjacent sequences.<ref name="pmid2738923">{{cite journal | vauthors = Pennings S, Muyldermans S, Meersseman G, Wyns L | title = Formation, stability and core histone positioning of nucleosomes reassembled on bent and other nucleosome-derived DNA | journal = Journal of Molecular Biology | volume = 207 | issue = 1 | pages = 183–192 | date = May 1989 | pmid = 2738923 | doi = 10.1016/0022-2836(89)90449-X }}</ref> This repositioning does not require disruption of the histone octamer but is consistent with nucleosomes being able to "slide" along the DNA ''in cis''. [[CTCF]] binding sites act as nucleosome positioning anchors so that, when used to align various genomic signals, multiple flanking nucleosomes can be readily identified.<ref name="pmid18654629">{{cite journal | vauthors = Fu Y, Sinha M, Peterson CL, Weng Z | title = The insulator binding protein CTCF positions 20 nucleosomes around its binding sites across the human genome | journal = PLOS Genetics | volume = 4 | issue = 7 | pages = e1000138 | date = July 2008 | pmid = 18654629 | pmc = 2453330 | doi = 10.1371/journal.pgen.1000138 | veditors = Van Steensel B | doi-access = free }}</ref> Although nucleosomes are intrinsically mobile, eukaryotes have evolved a large family of ATP-dependent chromatin remodelling enzymes to alter chromatin structure, many of which do so via nucleosome sliding. Nucleosome sliding is one of the possible mechanism for large scale tissue specific expression of genes. The transcription start site for genes expressed in a particular tissue, are nucleosome depleted while, the same set of genes in other tissue where they are not expressed, are nucleosome bound.<ref name="pmid22821566">{{cite journal |display-authors=6 |vauthors=Bargaje R, Alam MP, Patowary A, Sarkar M, Ali T, Gupta S, Garg M, Singh M, Purkanti R, Scaria V, Sivasubbu S, Brahmachari V, Pillai B |date=October 2012 |title=Proximity of H2A.Z containing nucleosome to the transcription start site influences gene expression levels in the mammalian liver and brain |journal=Nucleic Acids Research |volume=40 |issue=18 |pages=8965–8978 |doi=10.1093/nar/gks665 |pmc=3467062 |pmid=22821566}}</ref>

===DNA site exposure===
Nucleosomal DNA is in equilibrium between a wrapped and unwrapped state. DNA within the nucleosome remains fully wrapped for only 250 ms before it is unwrapped for 10-50 ms and then rapidly rewrapped, as measured using time-resolved [[Förster resonance energy transfer|FRET]].<ref name="pmid15580276">{{cite journal | vauthors = Li G, Levitus M, Bustamante C, Widom J | title = Rapid spontaneous accessibility of nucleosomal DNA | journal = Nature Structural & Molecular Biology | volume = 12 | issue = 1 | pages = 46–53 | date = January 2005 | pmid = 15580276 | doi = 10.1038/nsmb869 | s2cid = 14540078 }}</ref> This implies that DNA does not need to be actively dissociated from the nucleosome but that there is a significant fraction of time during which it is fully accessible. Introducing a DNA-binding sequence within the nucleosome increases the accessibility of adjacent regions of DNA when bound.<ref name="pmid15258568">{{cite journal | vauthors = Li G, Widom J | title = Nucleosomes facilitate their own invasion | journal = Nature Structural & Molecular Biology | volume = 11 | issue = 8 | pages = 763–769 | date = August 2004 | pmid = 15258568 | doi = 10.1038/nsmb801 | s2cid = 11299024 }}</ref> 

This propensity for DNA within the nucleosome to "breathe" has important functional consequences for all DNA-binding proteins that operate in a chromatin environment.<ref name="pmid15580276"/> In particular, the dynamic breathing of nucleosomes plays an important role in restricting the advancement of [[RNA polymerase II]] during transcription elongation.<ref>{{cite journal | vauthors = Hodges C, Bintu L, Lubkowska L, Kashlev M, Bustamante C | title = Nucleosomal fluctuations govern the transcription dynamics of RNA polymerase II | journal = Science | volume = 325 | issue = 5940 | pages = 626–628 | date = July 2009 | pmid = 19644123 | pmc = 2775800 | doi = 10.1126/science.1172926 | bibcode = 2009Sci...325..626H }}</ref>

=== Nucleosome free region ===
Promoters of active genes have nucleosome free regions (NFR). This allows for promoter DNA accessibility to various proteins, such as transcription factors. Nucleosome free region typically spans for 200 nucleotides in ''S. cerevisiae''<ref>{{cite journal | vauthors = Yuan GC, Liu YJ, Dion MF, Slack MD, Wu LF, Altschuler SJ, Rando OJ | title = Genome-scale identification of nucleosome positions in S. cerevisiae | journal = Science | volume = 309 | issue = 5734 | pages = 626–630 | date = July 2005 | pmid = 15961632 | doi = 10.1126/science.1112178 | s2cid = 43625066 | bibcode = 2005Sci...309..626Y | doi-access = free }}</ref> Well-positioned nucleosomes form boundaries of NFR. These nucleosomes are called +1-nucleosome and −1-nucleosome and are located at canonical distances downstream and upstream, respectively, from transcription start site.<ref name="Understanding nucleosome dynamics">{{cite journal | vauthors = Lai WK, Pugh BF | title = Understanding nucleosome dynamics and their links to gene expression and DNA replication | journal = Nature Reviews. Molecular Cell Biology | volume = 18 | issue = 9 | pages = 548–562 | date = September 2017 | pmid = 28537572 | pmc = 5831138 | doi = 10.1038/nrm.2017.47 }}</ref> +1-nucleosome and several downstream nucleosomes also tend to incorporate H2A.Z histone variant.<ref name="Understanding nucleosome dynamics"/>