Editing Epigenetics (section)

==Definitions==
The term ''epigenesis'' has a generic meaning of "extra growth" that has been used in English since the 17th century.<ref>[[Oxford English Dictionary]]: "The word is used by W. Harvey, ''Exercitationes'' 1651, p. 148, and in the ''English Anatomical Exercitations'' 1653, p. 272. It is explained to mean ‘partium super-exorientium additamentum’, ‘the additament of parts budding one out of another’."</ref> In scientific publications, the term ''epigenetics'' started to appear in the 1930s (see Fig. on the right). However, its contemporary meaning emerged only in the 1990s.<ref name="Moore_2015">{{cite book | vauthors = Moore DS |title=The Developing Genome: An Introduction to Behavioral Epigenetics |date=2015 |publisher=Oxford University Press |isbn=978-0-19-992235-2 }}{{pn|date=March 2024}}</ref> 
[[File:EpigenByYear 1.png|thumb|Number of patent families and non-patent documents with the term "epigenetic*" by publication year]]

A definition of the concept of ''epigenetic trait'' as a "stably heritable phenotype resulting from changes in a chromosome without alterations in the DNA sequence" was formulated at a [[Cold Spring Harbor Laboratory|Cold Spring Harbor]] meeting in 2008,<ref name="pmid19339683"/> although alternate definitions that include non-heritable traits are still being used widely.<ref name="NIH">{{cite web |title=Overview |url=http://www.roadmapepigenomics.org/overview |work=NIH Roadmap Epigenomics Project |access-date=7 December 2013 |archive-date=21 November 2019 |archive-url=https://web.archive.org/web/20191121014029/http://www.roadmapepigenomics.org/overview |url-status=dead }}</ref>

===Waddington's canalisation, 1940s===
The hypothesis of epigenetic changes affecting the expression of [[chromosome]]s was put forth by the Russian biologist [[Nikolai Koltsov]].<ref>Morange M. ''La tentative de Nikolai Koltzoff (Koltsov) de lier génétique, embryologie et chimie physique'', J. Biosciences. 2011. V. 36. P. 211-214</ref> From the generic meaning, and the associated adjective ''epigenetic'', British embryologist [[C. H. Waddington]] coined the term ''epigenetics'' in 1942 as pertaining to ''[[epigenesis (biology)|epigenesis]]'', in parallel to [[Valentin Haecker]]'s 'phenogenetics' ({{lang|de|Phänogenetik}}).<ref name=waddington>{{cite journal| vauthors = Waddington CH | title=The epigenotype| journal=Endeavour | volume=1 | pages=18–20 | year=1942 }}
"For the purpose of a study of inheritance, the relation between phenotypes and genotypes [...] is, from a wider biological point of view, of crucial importance, since it is the kernel of the whole problem of development."
</ref> ''Epigenesis'' in the context of the biology of that period referred to the [[cellular differentiation|differentiation]] of cells from their initial [[totipotent]] state during [[embryonic development]].<ref>See ''[[preformationism]]'' for historical background. ''[[Oxford English Dictionary]]'':
"the theory that the germ is brought into existence (by successive accretions), and not merely developed, in the process of reproduction. [...] The opposite theory was formerly known as the 'theory of evolution'; to avoid the ambiguity of this name, it is now spoken of chiefly as the 'theory of preformation', sometimes as that of 'encasement' or 'emboîtement'."</ref>

When Waddington coined the term, the physical nature of [[gene]]s and their role in heredity was not known. He used it instead as a conceptual model of how genetic components might interact with their surroundings to produce a [[phenotype]]; he used the phrase "[[epigenetic landscape]]" as a metaphor for [[morphogenesis|biological development]]. Waddington held that cell fates were established during development in a process he called [[canalisation (genetics)|canalisation]] much as a marble rolls down to the point of [[local optimum|lowest local elevation]].<ref name="Waddington2014">{{cite book | vauthors = Waddington CH |title=The Epigenetics of Birds |date=2014 |publisher=Cambridge University Press |isbn=978-1-107-44047-0 }}{{page needed|date=January 2020}}</ref> Waddington suggested visualising increasing irreversibility of cell type differentiation as ridges rising between the valleys where the marbles (analogous to cells) are travelling.<ref>{{cite journal | vauthors = Hall BK | title = In search of evolutionary developmental mechanisms: the 30-year gap between 1944 and 1974 | journal = Journal of Experimental Zoology Part B: Molecular and Developmental Evolution | volume = 302 | issue = 1 | pages = 5–18 | date = January 2004 | pmid = 14760651 | doi = 10.1002/jez.b.20002 | bibcode = 2004JEZ...302....5H | doi-access = free }}</ref>

In recent times, Waddington's notion of the epigenetic landscape has been rigorously formalized in the context of the [[system dynamics|systems dynamics]] state approach to the study of cell-fate.<ref>{{cite journal | vauthors = Alvarez-Buylla ER, Chaos A, Aldana M, Benítez M, Cortes-Poza Y, Espinosa-Soto C, Hartasánchez DA, Lotto RB, Malkin D, Escalera Santos GJ, Padilla-Longoria P | title = Floral morphogenesis: stochastic explorations of a gene network epigenetic landscape | journal = PLOS ONE | volume = 3 | issue = 11 | pages = e3626 | date = 3 November 2008 | pmid = 18978941 | pmc = 2572848 | doi = 10.1371/journal.pone.0003626 | bibcode = 2008PLoSO...3.3626A | doi-access = free }}</ref><ref name="sciencedirect.com">{{cite journal | vauthors = Rabajante JF, Babierra AL | title = Branching and oscillations in the epigenetic landscape of cell-fate determination | journal = Progress in Biophysics and Molecular Biology | volume = 117 | issue = 2–3 | pages = 240–249 | date = March 2015 | pmid = 25641423 | doi = 10.1016/j.pbiomolbio.2015.01.006 | s2cid = 2579314 }}</ref> Cell-fate determination is predicted to exhibit certain dynamics, such as attractor-convergence (the attractor can be an equilibrium point, limit cycle or [[strange attractor]]) or oscillatory.<ref name="sciencedirect.com"/>

===Contemporary===
In 1990, [[Robin Holliday]] defined epigenetics as "the study of the mechanisms of temporal and spatial control of gene activity during the development of complex organisms."<ref name="pmid2265224">{{cite journal | vauthors = Holliday R | title = DNA methylation and epigenetic inheritance | journal = Philosophical Transactions of the Royal Society of London. Series B, Biological Sciences | volume = 326 | issue = 1235 | pages = 329–38 | date = January 1990 | pmid = 1968668 | doi = 10.1098/rstb.1990.0015 | bibcode = 1990RSPTB.326..329H | doi-access = free }}</ref>

More recent usage of the word in biology follows stricter definitions. As defined by [[Arthur Riggs (geneticist)|Arthur Riggs]] and colleagues, it is "the study of [[mitosis|mitotically]] and/or [[meiosis|meiotically]] heritable changes in gene function that cannot be explained by changes in DNA sequence."<ref name="isbn0-87969-490-4">{{cite book |vauthors=Riggs AD, Martienssen RA, Russo VE | title=Epigenetic mechanisms of gene regulation | publisher=Cold Spring Harbor Laboratory Press | location=Plainview, NY | year=1996 | pages=1–4| isbn=978-0-87969-490-6 }}{{page needed|date=August 2013}}</ref>

The term has also been used, however, to describe processes which have not been demonstrated to be heritable, such as some forms of histone modification. Consequently, there are attempts to redefine "epigenetics" in broader terms that would avoid the constraints of requiring [[heritability]]. For example, [[Adrian Peter Bird|Adrian Bird]] defined epigenetics as "the structural adaptation of chromosomal regions so as to register, signal or perpetuate altered activity states."<ref name="pmid17522671" /> This definition would be inclusive of transient modifications associated with [[DNA repair]] or [[cell-cycle]] phases as well as stable changes maintained across multiple cell generations, but exclude others such as templating of membrane architecture and [[prions]] unless they impinge on chromosome function. Such redefinitions however are not universally accepted and are still subject to debate.<ref name="nature2008">{{cite journal | vauthors = Ledford H | title = Language: Disputed definitions | journal = Nature | volume = 455 | issue = 7216 | pages = 1023–8 | date = October 2008 | pmid = 18948925 | doi = 10.1038/4551023a | doi-access = free }}</ref> The [[National Institutes of Health|NIH]] "Roadmap Epigenomics Project", which ran from 2008 to 2017, uses the following definition: "For purposes of this program, epigenetics refers to both heritable changes in gene activity and [[gene expression|expression]] (in the progeny of cells or of individuals) and also stable, long-term alterations in the transcriptional potential of a cell that are not necessarily heritable."<ref>{{cite journal | vauthors = Gibney ER, Nolan CM | title = Epigenetics and gene expression | journal = Heredity | volume = 105 | issue = 1 | pages = 4–13 | date = July 2010 | pmid = 20461105 | doi = 10.1038/hdy.2010.54 | s2cid = 31611763 | doi-access = free }}</ref> In 2008, a consensus definition of the epigenetic trait, a "stably heritable phenotype resulting from changes in a chromosome without alterations in the DNA sequence," was made at a [[Cold Spring Harbor Laboratory|Cold Spring Harbor]] meeting.<ref name="pmid19339683">{{cite journal | vauthors = Berger SL, Kouzarides T, Shiekhattar R, Shilatifard A | title = An operational definition of epigenetics | journal = Genes & Development | volume = 23 | issue = 7 | pages = 781–3 | date = April 2009 | pmid = 19339683 | pmc = 3959995 | doi = 10.1101/gad.1787609 }}</ref>

The similarity of the word to "genetics" has generated many parallel usages. The "[[epigenome]]" is a parallel to the word "[[genome]]", referring to the overall epigenetic state of a cell, and [[epigenomics]] refers to global analyses of epigenetic changes across the entire genome.<ref name="NIH"/> The phrase "[[genetic code]]" has also been adapted – the "[[epigenetic code]]" has been used to describe the set of epigenetic features that create different phenotypes in different cells from the same underlying DNA sequence. Taken to its extreme, the "epigenetic code" could represent the total state of the cell, with the position of each molecule accounted for in an ''epigenomic map'', a diagrammatic representation of the gene expression, DNA methylation and histone modification status of a particular genomic region. More typically, the term is used in reference to systematic efforts to measure specific, relevant forms of epigenetic information such as the [[histone code hypothesis|histone code]] or [[DNA methylation]] patterns.{{citation needed|date=April 2019}}