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      The social construction of the social epigenome and the larger biological context

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          Abstract

          Epigenetics researchers in developmental, cell, and molecular biology greatly diverge in their understanding and definitions of epigenetics. In contrast, social epigeneticists, e.g., sociologists, scholars of STS, and behavioural scientists, share a focus and definition of epigenetics that is environmentally caused and trans-generationally inherited. This article demonstrates that this emphasis on the environment and on so-called Lamarckian inheritance, in addition to other factors, reflects an interdisciplinary power struggle with genetics, in which epigenetics appears to grant the social sciences a higher epistemic status. Social scientists’ understanding of epigenetics, thus, appears in part to be socially constructed, i.e., the result of extra-scientific factors, such as social processes and the self-interest of the discipline. This article argues that social epigeneticists make far-reaching claims by selecting elements from research labelled epigenetics in biology while ignoring widely confirmed scientific facts in genetics and cell biology, such as the dependence of epigenetic marks on DNA sequence-specific events, or the lack of evidence for the lasting influence of the environment on epigenetic marks or the epigenome. Moreover, they treat as a given crucial questions that are far from resolved, such as what role, if any, DNA methylation plays in the complex biochemical system of regulating gene activity. The article also points out incorrect perceptions and media hypes among biological epigeneticists and calls attention to an apparent bias among scientific journals that prefer papers that promote transgenerational epigenetic inheritance over articles that critique it. The article concludes that while research labelled epigenetics contributes significantly to our knowledge about chromatin and the genome, it does not, as is often claimed, rehabilitate Lamarck or overthrow the fundamental biological principles of gene regulation, which are based on specific regulatory sequences of the genome.

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          Most cited references45

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          A genome-wide housekeeping role for TFIID and a highly regulated stress-related role for SAGA in Saccharomyces cerevisiae.

          TFIID and SAGA share a common set of TAFs, regulate chromatin, and deliver TBP to promoters. Here we examine their relationship within the context of the Saccharomyces cerevisiae genome-wide regulatory network. We find that while TFIID and SAGA make overlapping contributions to the expression of all genes, TFIID function predominates at approximately 90% and SAGA at approximately 10% of the measurable genome. Strikingly, SAGA-dominated genes are largely stress induced and TAF independent, and are downregulated by the coordinate action of a variety of chromatin, TBP, and RNA polymerase II regulators. In contrast, the TFIID-dominated class is less regulated, but is highly dependent upon TAFs, including those shared between TFIID and SAGA. These two distinct modes of transcription regulation might reflect the need to balance inducible stress responses with the steady output of housekeeping genes.
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            DNA methylation and DNA methyltransferases

            The prevailing views as to the form, function, and regulation of genomic methylation patterns have their origin many years in the past, at a time when the structure of the mammalian genome was only dimly perceived, when the number of protein-encoding mammalian genes was believed to be at least five times greater than the actual number, and when it was not understood that only ~10% of the genome is under selective pressure and likely to have biological function. We use more recent findings from genome biology and whole-genome methylation profiling to provide a reappraisal of the shape of genomic methylation patterns and the nature of the changes that they undergo during gametogenesis and early development. We observe that the sequences that undergo deep changes in methylation status during early development are largely sequences without regulatory function. We also discuss recent findings that begin to explain the remarkable fidelity of maintenance methylation. Rather than a general overview of DNA methylation in mammals (which has been the subject of many reviews), we present a new analysis of the distribution of methylated CpG dinucleotides across the multiple sequence compartments that make up the mammalian genome, and we offer an updated interpretation of the nature of the changes in methylation patterns that occur in germ cells and early embryos. We discuss the cues that might designate specific sequences for demethylation or de novo methylation during development, and we summarize recent findings on mechanisms that maintain methylation patterns in mammalian genomes. We also describe the several human disorders, each very different from the other, that are caused by mutations in DNA methyltransferase genes.
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              The evolution of hierarchical gene regulatory networks.

              Comparative developmental evidence indicates that reorganizations in developmental gene regulatory networks (GRNs) underlie evolutionary changes in animal morphology, including body plans. We argue here that the nature of the evolutionary alterations that arise from regulatory changes depends on the hierarchical position of the change within a GRN. This concept cannot be accomodated by microevolutionary nor macroevolutionary theory. It will soon be possible to investigate these ideas experimentally, by assessing the effects of GRN changes on morphological evolution.
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                Author and article information

                Contributors
                uted@post.bgu.ac.il
                Journal
                Epigenetics Chromatin
                Epigenetics Chromatin
                Epigenetics & Chromatin
                BioMed Central (London )
                1756-8935
                23 September 2020
                23 September 2020
                2020
                : 13
                : 37
                Affiliations
                GRID grid.7489.2, ISNI 0000 0004 1937 0511, Jacques Loeb Centre for the History and Philosophy of the Life Sciences, , Ben-Gurion University of the Negev, ; P.O. Box 653, Beer Sheva, 8410500 Israel
                Author information
                http://orcid.org/0000-0003-0990-2337
                Article
                360
                10.1186/s13072-020-00360-w
                7510271
                c138b647-dfd3-4308-859f-6f8e47250a1c
                © The Author(s) 2020

                Open AccessThis article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/. The Creative Commons Public Domain Dedication waiver ( http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated in a credit line to the data.

                History
                : 17 May 2020
                : 15 September 2020
                Categories
                Research
                Custom metadata
                © The Author(s) 2020

                Genetics
                social epigenetics,environmental epigenetics,transgenerational epigenetic inheritance,cytosine methylation as genomic defense system,transcription factors,cellular memory

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