title: Epigenetic memory in response to environmental stressors.
abstract: Exposure to environmental stressors, toxicants, and nutrient deficiencies can affect DNA in several ways. Some exposures cause damage and alter the structure of DNA, but there is increasing evidence that the same or other environmental exposures, including those that occur during fetal developmentin utero, can cause epigenetic effects that 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 exposures to other 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. Although these changes seem to be mainly adaptive, they are also implicated in the pathogenesis and onset of diseases, depending on individual genotypic background and 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.-Vineis, P., Chatziioannou, A., Cunliffe, V. T., Flanagan, J. M., Hanson, M., Kirsch-Volders, M., Kyrtopoulos, S. Epigenetic memory in response to environmental stressors.
authors.affiliation: Medical Research Council-Public Health England Center for Environment and Health, Imperial College London, London, United Kingdom; p.vineis@imperial.ac.uk.
authors.forename: Paolo
authors.initials: P
authors.lastname: Vineis
authors.affiliation: Institute of Biology, Medicinal Chemistry, and Biotechnology, National Hellenic Research Foundation, Athens, Greece.
authors.forename: Aristotelis
authors.initials: A
authors.lastname: Chatziioannou
authors.affiliation: Department of Biomedical Science, University of Sheffield, Sheffield, United Kingdom.
authors.forename: Vincent T
authors.initials: VT
authors.lastname: Cunliffe
authors.affiliation: Epigenetics Unit, Department of Surgery and Cancer, Imperial College London, London, United Kingdom.
authors.forename: James M
authors.initials: JM
authors.lastname: Flanagan
authors.affiliation: Institute of Developmental Sciences, University Hospital Southampton, University of Southampton, United Kingdom.
authors.forename: Mark
authors.initials: M
authors.lastname: Hanson
authors.affiliation: Laboratory of Cell Genetics, Vrije Universiteit Brussels, Brussels, Belgium.
authors.forename: Micheline
authors.initials: M
authors.lastname: Kirsch-Volders
authors.affiliation: Institute of Biology, Medicinal Chemistry, and Biotechnology, National Hellenic Research Foundation, Athens, Greece.
authors.forename: Soterios
authors.initials: S
authors.lastname: Kyrtopoulos
mesh_terms: D000818:Animals; D019175:DNA Methylation / Q000187:drug effects / Q000502:physiology; D004777:Environment; D004781:Environmental Exposure; D004785:Environmental Pollutants / Q000633:toxicity*; D044127:Epigenesis, Genetic / Q000187:drug effects* / Q000502:physiology*; D006801:Humans
chemical_list: D004785:Environmental Pollutants
keywords: DNA methylation; environmental exposures; genes