Linking the Epigenome with Exposure Effects and Susceptibility: The Epigenetic Seed and Soil Model

Abstract

The epigenome is a dynamic mediator of gene expression that shapes the way that cells, tissues, and organisms respond to their environment. Initial studies in the emerging field of "toxicoepigenetics" have described either the impact of an environmental exposure on the epigenome or the association of epigenetic signatures with the onset or progression of disease; however, the majority of these pioneering studies examined the relationship between discrete epigenetic modifications and the effects of a single environmental factor. Although these data provide critical blocks with which we construct our understanding of the role of the epigenome in susceptibility and disease, they are akin to individual letters in a complex alphabet that is used to compose the language of the epigenome. Advancing the use of epigenetic data to gain a more comprehensive understanding of the mechanisms underlying exposure effects, identify susceptible populations, and inform the next generation risk assessment depends on our ability to integrate these data in a way that accounts for their cumulative impact on gene regulation. Here we will review current examples demonstrating associations between the epigenetic impacts of intrinsic factors, such as such as age, genetics, and sex, and environmental exposures shape the epigenome and susceptibility to exposure effects and disease. We will also demonstrate how the "epigenetic seed and soil" model can be used as a conceptual framework to explain how epigenetic states are shaped by the cumulative impacts of intrinsic and extrinsic factors and how these in turn determine how an individual responds to subsequent exposure to environmental stressors.

ERK1/2 and p38 regulate inter-individual variability in ozone-mediated IL-8 gene expression in primary human bronchial epithelial cells

“…While our data suggest that epithelial cell responses are conserved in a donor-specific fashion, the basis of this ‘programming’ remains to be determined. While it may simply reflect genetic variability, it is possible that epithelial cells may retain an epigenetic imprint of their donor’s life history that can determine future responsiveness 16 . Although the factors that ultimately determine ozone-associated IL-8 induction in epithelial cells are unclear, our findings suggest that the differential activation of MAPKs is likely a part of this programming.…”

Consequences of early life stress on genomic landscape of H3K4me3 in prefrontal cortex of adult mice

“…Epigenetic processes such as DNA methylation and post-translational histone modifications are known to play key roles in memorizing of environmental influences [ 20 , 21 ]. In this way, epigenetic modifications could potentially mediate embedding early social exposure in the genome and provide the long-lasting nature of induced changes in neurobiology and behavior [ 4 , 22 , 23 ].…”

Why we need a National Living Soil Repository

“…However, the majority of soil microbial community studies currently ignores plasmids and focuses only on analyses of genomic DNA and often a single gene, such as the ribosomal RNA gene. Even more recently, research in the nascent field of epigenetics has shown that plant markers, such as DNA methylation, are influenced by environmental factors (11). Yet, we are unaware of any studies that have assessed the role of epigenetics in a system with the complexity of organisms found in soil.…”