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Epigenetics
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===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 = 329β38 | 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=1β4| 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 = 1023β8 | 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 = 4β13 | 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 = 781β3 | 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 β 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}}
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