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closeCaveat: Distinct meaning of 'EPIGENETIC'
Posted by SuiHuang on 05 Jul 2016 at 16:07 GMT
Great article. Finally someone says it loud and clear: "Epigenetics" as understood here (and by many, but incompletely, see below) is just one layer of the phenotype. There is in principle no fundamental difference between an epigenetic mark (DNA methylation) and say, expression of a transcription factor, or the phosphorylation of a protein (also covalent!). All these features can be stable across cell generations, even organismal generations, with some characteristic decay rate. (DNA methylation in rapidly lost in some cells after just a few cell generations)
An important aspect not centrally considered here (expect in the context of pointing to the fact that genetic markers are RANDOM) is that the epigenetic marks, much as any expression marker, or protein modification are physically not independent from each other unlike genetic mutations. Genetic variants that arise from mutations are (in general, if one believes in Darwinism more than Lamarckism) officially still random and at is: agnostic of environment and of OTHER loci. This is not the case for expression of any protein or for DNA methylation or any chromatin modification since the locus is informed by the expression of the transcription factors that recruit the modifying enzymes (and of course are encoded somewhere else in the genome). Thus, DNA methylation is the manifestation of a network of activities at various loci - this links it to a second type of epigenetics discussed below.
Thus, the epigenetic marks as understood in the kind of studies discussed here represent some mapping of the gene expression profile. No more. And the gene expression profile is of course highly constrained by the gene regulatory network that consist of locus-locus interactions.
This brings us back to the term epigenetics and why there are two distinct meanings:
'Epigenetics' was originally coined by Waddington in the 1940s in conjunction with a NETWORK of genetic causes.
The modern version of this more holistic understanding then is that epigenetic states are attractor states in a non-linear system of regulatory interaction. The attractor stabilize gene expression profiles such a given profile is self-sustaining nd can self-regenerate after cell division ( and then is mapped back to establish the same DNA methylation pattern). Only in the 1970s have molecular biologists, upon discovery of DNA methylation, hijacked the term EPIGENETICS and used it to mean DNA methylation and later, chromatin modifications..
There is thus a vast confusion among biologists going on, that even journal editors and funding agencies are not aware of because most people are not aware of these two meanings of the term "EPIGENETICS":
(a) Waddington's original meaning, and in the modern version, referring to gene regulatory networks mediated by transcription factors that give rise to self-sustaining gene expression profile (DNA methylation here is not necessary as the examples of Drosophila and C. elegans show)
(b) The molecular meaning, referring mainly to DNA methylation (and sometimes to chromatin modifications) as used in the Epigenome Roadmap, and all the relate studies, claiming some particular meaning of the epigenetic markers, as in EWAS , discussed in t is article.
No meaningful discussion can take place before one internalizes these two meanings!
Mark Ptashne has eloquently pointed to the meaninglessness of the term epigenetics in the sense of (b):
http://www.ncbi.nlm.nih.g...
For a historical more encompassing (but still incomplete) overview and explanation of the modern non-linear dynamnics view, that goes back to Waddington, see:
http://biorxiv.org/conten...
RE: Caveat: Distinct meaning of 'EPIGENETIC'
greally replied to SuiHuang on 05 Jul 2016 at 19:17 GMT
Thanks Dr. Huang. Your cited bioRxiv article is certainly one of the most insightful historical appraisals of the derivation of the word 'epigenetics.' We were constrained by space in this review and could not get into the details about the variable use of the term 'epigenetics,' but it is certainly the case that it is of critical importance to define what you mean by the term before you apply it.