Definitions of epigenetics

The term epigenetics in its contemporary usage emerged in the 1990s, but for some years has been used with somewhat variable meanings. A consensus 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 meeting in 2008, although alternate definitions that include non-heritable traits are still being used.

When Waddington coined the term, the physical nature of genes 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 biological development. Waddington held that cell fates were established during development in a process he called canalisation much as a marble rolls down to the point of lowest local elevation. Waddington suggested visualising increasing irreversibility of cell type differentiation as ridges rising between the valleys where the marbles (analogous to cells) are travelling.

In recent times, Waddington's notion of the epigenetic landscape has been rigorously formalized in the context of the systems dynamics state approach to the study of cell-fate. 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.

Robin Holliday defined epigenetics as "the study of the mechanisms of temporal and spatial control of gene activity during the development of complex organisms." Thus, in its broadest sense, epigenetic can be used to describe anything other than DNA sequence that influences the development of an organism.

More recent usage of the word in biology follows stricter definitions. It is, as defined by Arthur Riggs and colleagues, "the study of mitotically and/or meiotically heritable changes in gene function that cannot be explained by changes in DNA sequence."

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; there are therefore attempts to redefine "epigenetics" in broader terms that would avoid the constraints of requiring heritability. For example, Adrian Bird defined epigenetics as "the structural adaptation of chromosomal regions so as to register, signal or perpetuate altered activity states." 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. The NIH "Roadmap Epigenomics Project", ongoing as of 2016, uses the following definition: "For purposes of this program, epigenetics refers to both heritable changes in gene activity and 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." 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 meeting.

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. 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 or DNA methylation patterns.

In a sense somewhat unrelated to its use in biological disciplines, the term "epigenetic" has also been used in developmental psychology to describe psychological development as the result of an ongoing, bi-directional interchange between heredity and the environment. Interactivist ideas of development have been discussed in various forms and under various names throughout the 19th and 20th centuries. An early version was proposed, among the founding statements in embryology, by Karl Ernst von Baer and popularized by Ernst Haeckel. A radical epigenetic view (physiological epigenesis) was developed by Paul Wintrebert. Another variation, probabilistic epigenesis, was presented by Gilbert Gottlieb in 2003. This view encompasses all of the possible developing factors on an organism and how they not only influence the organism and each other, but how the organism also influences its own development.

The developmental psychologist Erik Erikson wrote of an epigenetic principle in his 1968 book Identity: Youth and Crisis, encompassing the notion that we develop through an unfolding of our personality in predetermined stages, and that our environment and surrounding culture influence how we progress through these stages. This biological unfolding in relation to our socio-cultural settings is done in stages of psychosocial development, where "progress through each stage is in part determined by our success, or lack of success, in all the previous stages.