Editing Epigenetics (section)

===Development===
{{See also|Epigenetics of human development}}
Developmental epigenetics can be divided into predetermined and probabilistic epigenesis. Predetermined epigenesis is a unidirectional movement from structural development in DNA to the functional maturation of the protein. "Predetermined" here means that development is scripted and predictable. Probabilistic epigenesis on the other hand is a bidirectional structure-function development with experiences and external molding development.<ref name=Griesemer_2005>{{cite journal | vauthors=Griesemer J, Haber MH, Yamashita G, Gannett L | title=Critical Notice: Cycles of Contingency – Developmental Systems and Evolution | journal=Biology & Philosophy |date=March 2005 | volume=20 | issue =2–3 | pages=517–44 | doi=10.1007/s10539-004-0836-4| s2cid=2995306 }}</ref>

Somatic epigenetic inheritance, particularly through DNA and histone covalent modifications and [[nucleosome]] repositioning, is very important in the development of multicellular eukaryotic organisms.<ref name="Teif_2014"/> The genome sequence is static (with some notable exceptions), but cells differentiate into many different types, which perform different functions, and respond differently to the environment and intercellular signaling. Thus, as individuals develop, [[morphogen]]s activate or silence genes in an epigenetically heritable fashion, giving cells a memory. In mammals, most cells terminally differentiate, with only [[stem cells]] retaining the ability to differentiate into several cell types ("totipotency" and "multipotency"). In [[mammal]]s, some stem cells continue producing newly differentiated cells throughout life, such as in [[Epigenetic Regulation of Neurogenesis|neurogenesis]], but mammals are not able to respond to loss of some tissues, for example, the inability to regenerate limbs, which some other animals are capable of. Epigenetic modifications regulate the transition from neural stem cells to glial progenitor cells (for example, differentiation into oligodendrocytes is regulated by the deacetylation and methylation of histones).<ref>Chapter: "Nervous System Development" in "Epigenetics," by Benedikt Hallgrimsson and Brian Hall</ref> Unlike animals, plant cells do not terminally differentiate, remaining totipotent with the ability to give rise to a new individual plant. While plants do utilize many of the same epigenetic mechanisms as animals, such as [[chromatin remodeling]], it has been hypothesized that some kinds of plant cells do not use or require "cellular memories", resetting their gene expression patterns using positional information from the environment and surrounding cells to determine their fate.<ref name="pmid17194589">{{cite journal | vauthors = Costa S, Shaw P | title = 'Open minded' cells: how cells can change fate | journal = Trends in Cell Biology | volume = 17 | issue = 3 | pages = 101–6 | date = March 2007 | pmid = 17194589 | doi = 10.1016/j.tcb.2006.12.005 | url = http://cromatina.icb.ufmg.br/biomol/seminarios/outros/grupo_open.pdf | url-status = dead | quote = This might suggest that plant cells do not use or require a cellular memory mechanism and just respond to positional information. However, it has been shown that plants do use cellular memory mechanisms mediated by PcG proteins in several processes, ... (p. 104) | archive-url = https://web.archive.org/web/20131215042638/http://cromatina.icb.ufmg.br/biomol/seminarios/outros/grupo_open.pdf | df = dmy-all | archive-date = 15 December 2013 }}</ref>

Epigenetic changes can occur in response to environmental exposure – for example, maternal dietary supplementation with [[genistein]] (250&nbsp;mg/kg) have epigenetic changes affecting expression of the [[agouti gene]], which affects their fur color, weight, and propensity to develop cancer.<ref name="pmid12163699">{{cite journal | vauthors = Cooney CA, Dave AA, Wolff GL | title = Maternal methyl supplements in mice affect epigenetic variation and DNA methylation of offspring | journal = The Journal of Nutrition | volume = 132 | issue = 8 Suppl | pages = 2393S–2400S | date = August 2002 | pmid = 12163699 | doi = 10.1093/jn/132.8.2393S | doi-access = free }}</ref><ref name="waterland">{{cite journal | vauthors = Waterland RA, Jirtle RL | title = Transposable elements: targets for early nutritional effects on epigenetic gene regulation | journal = Molecular and Cellular Biology | volume = 23 | issue = 15 | pages = 5293–300 | date = August 2003 | pmid = 12861015 | pmc = 165709 | doi = 10.1128/MCB.23.15.5293-5300.2003 }}</ref><ref>{{cite journal | vauthors = Dolinoy DC | title = The agouti mouse model: an epigenetic biosensor for nutritional and environmental alterations on the fetal epigenome | journal = Nutrition Reviews | volume = 66 | issue = Suppl 1 | pages = S7-11 | date = August 2008 | pmid = 18673496 | pmc = 2822875 | doi = 10.1111/j.1753-4887.2008.00056.x }}</ref> Ongoing research is focused on exploring the impact of other known [[teratogen]]s, such as [[diabetic embryopathy]], on [[methylation]] signatures.<ref>{{cite journal | vauthors = Schulze KV, Bhatt A, Azamian MS, Sundgren NC, Zapata GE, Hernandez P, Fox K, Kaiser JR, Belmont JW, Hanchard NA | title = Aberrant DNA methylation as a diagnostic biomarker of diabetic embryopathy | journal = Genetics in Medicine | volume = 21 | issue = 11 | pages = 2453–2461 | date = November 2019 | pmid = 30992551 | doi = 10.1038/s41436-019-0516-z | s2cid = 116880337 | doi-access = free }}</ref>

Controversial results from one study suggested that traumatic experiences might produce an epigenetic signal that is capable of being passed to future generations. Mice were trained, using foot shocks, to fear a cherry blossom odor. The investigators reported that the mouse offspring had an increased aversion to this specific odor.<ref>{{cite web | url = https://www.scientificamerican.com/article/fearful-memories-passed-down/ | title = Fearful Memories Passed Down to Mouse Descendants: Genetic imprint from traumatic experiences carries through at least two generations | vauthors = Callaway E | work = Nature Magazine | date = 1 December 2013 | via = Scientific American }}</ref><ref>{{cite web | url = http://medicalxpress.com/news/2013-12-mice-sons-grandsons-dangers-sperm.html#ajTabs | title = Mice can 'warn' sons, grandsons of dangers via sperm | vauthors = Le Roux M | date = 13 December 2013 }}</ref> They suggested epigenetic changes that increase gene expression, rather than in DNA itself, in a gene, M71, that governs the functioning of an odor receptor in the nose that responds specifically to this cherry blossom smell. There were physical changes that correlated with olfactory (smell) function in the brains of the trained mice and their descendants. Several criticisms were reported, including the study's low statistical power as evidence of some irregularity such as bias in reporting results.<ref name="Francis_2014">{{cite journal | vauthors = Francis G | title = Too much success for recent groundbreaking epigenetic experiments | journal = Genetics | volume = 198 | issue = 2 | pages = 449–451 | date = October 2014 | pmid = 25316784 | pmc = 4196602 | doi = 10.1534/genetics.114.163998 }}</ref> Due to limits of sample size, there is a probability that an effect will not be demonstrated to within statistical significance even if it exists. The criticism suggested that the probability that all the experiments reported would show positive results if an identical protocol was followed, assuming the claimed effects exist, is merely 0.4%. The authors also did not indicate which mice were siblings, and treated all of the mice as statistically independent.<ref>{{cite journal | vauthors = Dias BG, Ressler KJ | title = Parental olfactory experience influences behavior and neural structure in subsequent generations | journal = Nature Neuroscience | volume = 17 | issue = 1 | pages = 89–96 | date = January 2014 | pmid = 24292232 | pmc = 3923835 | doi = 10.1038/nn.3594 }} (see comment by Gonzalo Otazu)</ref> The original researchers pointed out negative results in the paper's appendix that the criticism omitted in its calculations, and undertook to track which mice were siblings in the future.<ref>{{Cite web | url=http://www.the-scientist.com/?articles.view/articleNo/41239/title/Epigenetics-Paper-Raises-Questions/ | title=Epigenetics Paper Raises Questions}}</ref>