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Complex Phenotypes: Epigenetic Manifestation of Environmental Exposures

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Environmental Epigenomics in Health and Disease

Part of the book series: Epigenetics and Human Health ((EHH))

Abstract

Environmental influences in early development alter the epigenome and lead to complex phenotypes and disease susceptibility throughout the life course. Five primary factors, including nutrition, behavior, stress, toxins, and stochasticity, act to influence the epigenome during this critical period. To illustrate how changes in early environment can dramatically affect the epigenome, we provide examples from diverse members of the animal kingdom, spanning insects to human. Specific to mammalian early embryogenesis, DNA methylation, and other epigenetic marks are reset at two specific times in distinct cell lineages leading to epigenetic programming of gametic and somatic cells. These two waves of genomic demethylation and reestablishment of methylation frame the sensitive times for early environmental influences. Evaluating the complex effects of environmental exposures on the developing epigenome requires novel and comprehensive approaches. In this chapter we outline a strategy for the evaluation of environmentally induced epigenetic effects across animal models and human samples, highlighting the necessity for careful assessment of dose and resulting phenotypic changes across the life course. Herein we review the history, environmental factors, critical time points, and vulnerable genomic structures of epigenome–environment interactions. We also provide a framework to further explore epigenomic changes and translate this knowledge from mouse to man.

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Abbreviations

BPA:

Bisphenol A

CDK:

Cyclin-dependent kinase

DMR:

Differentially methylated region

DOHaD:

Developmental origins of health and disease

GR:

Glucocorticoid receptor

IAP:

Intracisternal A-particle

LTR:

Long terminal repeat

PGC:

Primordial germ cells

PRC2:

Polycomb repressive complex 2

RAMs:

Regions of altered methylation

tRNA:

Transfer RNA

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Acknowledgments

Research support was provided by NIH grants T32 ES007062 (CF), R01 ES017524 (DCD), and the University of Michigan NIEHS P30 Core Center ES017885 as well as NIH/EPA P20 grant ES018171/RD 83480001. The authors have no conflicts of interest and declare no competing financial interests.

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Authors and Affiliations

  1. Department of Environmental Health Sciences, School of Public Health, University of Michigan, 6630 Crossroads, 1415 Washington Heights, Ann Arbor, MI, 48109, USA

    Christopher Faulk & Dana C. Dolinoy

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  1. Christopher Faulk
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  2. Dana C. Dolinoy
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Correspondence to Dana C. Dolinoy .

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Editors and Affiliations

  1. School of Medicine and Public Health, McArdle Laboratory for Cancer Research, University of Wisconsin-Madison, University Avenue 1400, Madison, 53706, Wisconsin, USA

    Randy L Jirtle

  2. National Institute of Environmental Hea, NIEHS, National Institutes of Health, Research Triangle Park, 27709, North Carolina, USA

    Frederick L. Tyson

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Faulk, C., Dolinoy, D.C. (2013). Complex Phenotypes: Epigenetic Manifestation of Environmental Exposures. In: Jirtle, R., Tyson, F. (eds) Environmental Epigenomics in Health and Disease. Epigenetics and Human Health. Springer, Berlin, Heidelberg. https://doi.org/10.1007/978-3-642-23380-7_4

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