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Markers as mediators: A review and synthesis of epigenetics literature.

ABSTRACT: Epigenetics, the study of the processes that control gene expression without a change in DNA sequence, highlights the importance of environmental factors in gene regulation. This paper maps the terrain of epigenetics and identifies four main research subfields: gene expression; molecular epigenetics; clinical epigenetics and epigenetic epidemiology. Within and across these fields, we analyse of what is conceptualised as environment and demonstrate the variable ways authors understand epigenetics environments. Then, following an analysis of the discursive strategies employed by epigenetics researchers, we demonstrate how authors portray the interactions between genes, epigenetics, and environment as relationships linking the outside (where the environment is located) with the inside (where the genes are located). We argue that authors assign specific roles to each actor: the environment as the active player initiating the relationship, the genes as recipients, and epigenetics as mediators between environment and genes. Framed as mediators, epigenetic markers can be understood as enablers of communication between environment and genome, capable of processing and organising signals so as to regulate the interactions between the actors of epigenetic relationships. This finding complicates the observation by social science scholars that the interactions between environment and genes can be understood through the concept of signal.

SUBMITTER: Pinel C

PROVIDER: S-EPMC6520226 | biostudies-literature | 2019 May

REPOSITORIES: biostudies-literature

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Markers as mediators: A review and synthesis of epigenetics literature.

Pinel Clémence C Prainsack Barbara B McKevitt Christopher C

BioSocieties 20170918 1

Epigenetics, the study of the processes that control gene expression without a change in DNA sequence, highlights the importance of environmental factors in gene regulation. This paper maps the terrain of epigenetics and identifies four main research subfields: gene expression; molecular epigenetics; clinical epigenetics and epigenetic epidemiology. Within and across these fields, we analyse of what is conceptualised as environment and demonstrate the variable ways authors understand epigenetics ...[more]

PMID: 31105763

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Project description:It has widely accepted that 5-methylcytosine is the only form of DNA methylation in mammalian genomes, whereas the other forms, such as N6-methyladenine, primarily exist in prokaryotes and only a few eukaryotes. Herein, we demonstrated the surprising presence of N6-methyladenine in mammalian genomes, especially, mouse embryonic stem cells. This modification is enriched at histone variant H2A.X-deposited genomic regions in wild type embryonic stem cells. Our work also showed that a previously unknown DNA demethylase, Alkbh1, is the major demethylase for N6-methyladenine in embryonic stem cells. Increase of N6-methyladenine levels in Alkbh1 deficient cells leads to silencing of genes that regulate embryonic development. Surprisingly, genes located on the X-chromosome, but not the Y-chromosome or autosomes are preferentially silenced by N6-methyladenine. Strikingly, N6-methyladenine in Alkbh1 deficient cells are specifically deposition at young, full-length subfamilies of LINE1 transposons that are strongly enriched on the X chromosome. Furthermore, N6-methyladenine deposition on LINE1s pattern is inversely correlated with their evolutionary age. The deposition of N6-methyladenine results in epigenetic silencing of such L1s, which are otherwise actively transcribed in wild type embryonic stem cells, and the neighboring enhancers and genes. Furthermore, N6-methyladenine induced-silencing resists gene activation signals during embryonic stem cell differentiation. Thus, N6-methyladenine adopts a new function in epigenetic silencing in evolution, distinct from its role in gene activation in other organisms. In summary, our results demonstrate that N6-methyladenine unexpectedly constitutes a crucial component of the epigenetic regulation repertoire in mammalian genomes. First, we used different histone antibodies to enrich for DNA molecules with histone modification or specific variant in mouse ESCs as previously described Native-ChIP methods. Then, co-purified DNA molecules from WT or KO ESCs were subject to HiSeq2000 sequencing and data analysis for histone modification or variant peaks.

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Markers as mediators: A review and synthesis of epigenetics literature.

Publications

Markers as mediators: A review and synthesis of epigenetics literature.

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