Editing Epigenetics (section)

===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"/>