Epigenetic memory in response to environmental stressors

Abstract

eprints@whiterose.ac.uk https://eprints.whiterose.ac.uk/ Reuse Unless indicated otherwise, fulltext items are protected by copyright with all rights reserved. The copyright exception in section 29 of the Copyright, Designs and Patents Act 1988 allows the making of a single copy solely for the purpose of non-commercial research or private study within the limits of fair dealing. The publisher or other rights-holder may allow further reproduction and re-use of this version -refer to the White Rose Research Online record for this item. Where records identify the publisher as the copyright holder, users can verify any specific terms of use on the publisher's website. TakedownIf you consider content in White Rose Research Online to be in breach of UK law, please notify us by emailing eprints@whiterose.ac.uk including the URL of the record and the reason for the withdrawal request. 1 Draft August 3rd 2016Paolo Vineis (1), Aristotelis Chatziioannou (2), Vincent Cunliffe (3) Conflicts of interest: None declared 2 AbstractExposure to environmental stressors, toxicants and nutrient deficiencies can affect DNA in a number of ways. While some exposures cause damage and alter the structure of DNA, there is increasing evidence that the same or other environmental exposures, including those experienced during fetal development in utero, can cause epigenetic effects which modulate DNA function and gene expression. Some epigenetic changes to DNA that affect gene transcription are at least partially reversible (i.e. they can be enzymatically reversed after cessation of exposure to environmental agents), but some epigenetic modifications seem to persist even for decades. To explain the effects of early life experiences (such as famine and other exposures to stressors) on the long-term persistence of specific patterns of epigenetic modifications, such as DNA methylation, we propose an analogy with immune memory. We propose that an epigenetic memory can be established and maintained in self-renewing stem cell compartments. We suggest that the observations on early life effects on adult diseases and the persistence of methylation changes in smokers support our hypothesis, for which a mechanistic basis, however, needs to be further clarified. We outline a new model based on methylation changes. Though these changes seem to be mainly adaptive, they are also implicated in the pathogenesis and onset of diseases, depending on individual genotypic background and/or types of subsequent exposures. Elucidating the relationships between the adaptive and maladaptive consequences of the epigenetic modifications that result from complex environmental exposures is a major challenge for current and future research in epigenetics.

HDAC7‐mediated control of tumour microenvironment maintains proliferative and stemness competence of human mammary epithelial cells

“…Environmental adaptations require fine-tuning of gene transcription supervised by chromatin modifications. A repertoire of epigenetic regulators controls the milieu of the epigenetic marks that influence chromatin compaction or opening (Vineis et al, 2017). Among transcriptional repressors, class IIa HDACs are important regulators of genetic programmes, which orchestrate different cellular fates.…”

Surviving Starvation: AMPK Protects Germ Cell Integrity by Targeting Multiple Epigenetic Effectors

“…As these children aged, they developed a spectrum of disorders that had no obvious genetic history within their respective families. Later, alterations in the DNA methylation patterns were identified in these individuals that suggested that these disorders might be linked to the differential epigenetic modifications that were potentially written during this period of famine . Comparable findings have been observed for other populations in similar contexts around the world …”

“…Later, alterations in the DNA methylation patterns were identified in these individuals that suggested that these disorders might be linked to the differential epigenetic modifications that were potentially written during this period of famine. [1][2][3]6] Comparable findings have been observed for other populations in similar contexts around the world. [7] In a recent study, we examined how the AMP activated protein kinase (AMPK), which has been well described for its role in maintaining energy homeostasis in response to several stresses, [8,9] is also involved in blocking specific chromatin modifications and epigenetic changes in Caenorhabditis elegans larvae that are subjected to starvation.…”

“…In many organisms, environmental stressors can even impact descendants over multiple generations as a result of molecular changes recorded in a pattern of characteristic chromatin modifications that affect both gene expression and genome stability without altering DNA sequence. Perhaps one of the most striking cases of this kind of epigenetic adjustment was described in children born during, or shortly after, the infamous Dutch Hongerwinter that occurred in Nazi‐occupied Holland during the winter of 1944/45 . Children that were born of starved mothers were developmentally normal, although they were both smaller and weighed less than average .…”

“…[1][2][3] Children that were born of starved mothers were developmentally normal, although they were both smaller and weighed less than average. [1,2,4,5] As these children aged, they developed a spectrum of disorders that had no obvious genetic history within their respective families. Later, alterations in the DNA methylation patterns were identified in these individuals that suggested that these disorders might be linked to the differential epigenetic modifications that were potentially written during this period of famine.…”