Editing Cellular differentiation (section)

====Nucleosome positioning====
While the [[nucleic acid sequence|DNA sequence]] of most cells of an organism is the same, the binding patterns of transcription factors and the corresponding gene expression patterns are different. To a large extent, differences in transcription factor binding are determined by the chromatin accessibility of their binding sites through [[histone modification]] and/or [[pioneer factor]]s. In particular, it is important to know whether a [[nucleosome]] is covering a given genomic binding site or not. This can be determined using a [[chromatin immunoprecipitation]] assay.<ref>{{Cite web|url=http://www.bio.brandeis.edu/haberlab/jehsite/chIP.html|title=Chromatin Immuprecipitation|website=www.bio.brandeis.edu|access-date=2016-12-26|archive-date=2017-11-25|archive-url=https://web.archive.org/web/20171125204418/http://www.bio.brandeis.edu/haberlab/jehsite/chIP.html|url-status=dead}}</ref>

=====Histone acetylation and methylation=====
DNA-nucleosome interactions are characterized by two states: either tightly bound by nucleosomes and transcriptionally inactive, called [[heterochromatin]], or loosely bound and usually, but not always, transcriptionally active, called [[euchromatin]]. The epigenetic processes of histone methylation and acetylation, and their inverses demethylation and deacetylation primarily account for these changes. The effects of acetylation and deacetylation are more predictable. An acetyl group is either added to or removed from the positively charged Lysine residues in histones by enzymes called [[histone acetyltransferase]]s or [[histone deactylase]]s, respectively. The acetyl group prevents Lysine's association with the negatively charged DNA backbone. Methylation is not as straightforward, as neither methylation nor demethylation consistently correlate with either gene activation or repression. However, certain methylations have been repeatedly shown to either activate or repress genes. The trimethylation of lysine 4 on histone 3 (H3K4Me3) is associated with gene activation, whereas trimethylation of lysine 27 on histone 3 represses genes.<ref name="pmid12667454">{{cite journal | vauthors = Krogan NJ, Dover J, Wood A, Schneider J, Heidt J, Boateng MA, Dean K, Ryan OW, Golshani A, Johnston M, Greenblatt JF, Shilatifard A | title = The Paf1 complex is required for histone H3 methylation by COMPASS and Dot1p: linking transcriptional elongation to histone methylation | journal = Molecular Cell | volume = 11 | issue = 3 | pages = 721–729 | date = March 2003 | pmid = 12667454 | doi = 10.1016/S1097-2765(03)00091-1 | doi-access = free }}</ref><ref name="pmid12667453">{{cite journal | vauthors = Ng HH, Robert F, Young RA, Struhl K | title = Targeted recruitment of Set1 histone methylase by elongating Pol II provides a localized mark and memory of recent transcriptional activity | journal = Molecular Cell | volume = 11 | issue = 3 | pages = 709–719 | date = March 2003 | pmid = 12667453 | doi = 10.1016/S1097-2765(03)00092-3 | doi-access = free }}</ref><ref name="pmid15680324">{{cite journal | vauthors = Bernstein BE, Kamal M, Lindblad-Toh K, Bekiranov S, Bailey DK, Huebert DJ, McMahon S, Karlsson EK, Kulbokas EJ, Gingeras TR, Schreiber SL, Lander ES | title = Genomic maps and comparative analysis of histone modifications in human and mouse | journal = Cell | volume = 120 | issue = 2 | pages = 169–181 | date = January 2005 | pmid = 15680324 | doi = 10.1016/j.cell.2005.01.001 | s2cid = 7193829 | doi-access = free }}</ref>

=====In stem cells=====
{{further|Stem cell}}

During differentiation, stem cells change their gene expression profiles. Recent studies have implicated a role for nucleosome positioning and histone modifications during this process.<ref name = "Teif_et_al">{{cite journal | vauthors = Teif VB, Vainshtein Y, Caudron-Herger M, Mallm JP, Marth C, Höfer T, Rippe K | title = Genome-wide nucleosome positioning during embryonic stem cell development | journal = Nature Structural & Molecular Biology | volume = 19 | issue = 11 | pages = 1185–1192 | date = November 2012 | pmid = 23085715 | doi = 10.1038/nsmb.2419 | s2cid = 34509771 }}</ref> There are two components of this process: turning off the expression of embryonic stem cell (ESC) genes, and the activation of cell fate genes. Lysine specific demethylase 1 ([[LSD1|KDM1A]]) is thought to prevent the use of [[enhancer (genetics)|enhancer]] regions of pluripotency genes, thereby inhibiting their transcription.<ref name="ReferenceB">{{cite journal | vauthors = Whyte WA, Bilodeau S, Orlando DA, Hoke HA, Frampton GM, Foster CT, Cowley SM, Young RA | title = Enhancer decommissioning by LSD1 during embryonic stem cell differentiation | journal = Nature | volume = 482 | issue = 7384 | pages = 221–225 | date = February 2012 | pmid = 22297846 | pmc = 4144424 | doi = 10.1038/nature10805 | bibcode = 2012Natur.482..221W }}</ref> It interacts with [[NuRD|Mi-2/NuRD complex]] (nucleosome remodelling and histone deacetylase) complex,<ref name="ReferenceB"/> giving an instance where methylation and acetylation are not discrete and mutually exclusive, but intertwined processes.