Review Article | Published:

Epigenetics and the environment: emerging patterns and implications

Nature Reviews Genetics volume 13, pages 97109 (2012) | Download Citation

Abstract

Epigenetic phenomena in animals and plants are mediated by DNA methylation and stable chromatin modifications. There has been considerable interest in whether environmental factors modulate the establishment and maintenance of epigenetic modifications, and could thereby influence gene expression and phenotype. Chemical pollutants, dietary components, temperature changes and other external stresses can indeed have long-lasting effects on development, metabolism and health, sometimes even in subsequent generations. Although the underlying mechanisms remain largely unknown, particularly in humans, mechanistic insights are emerging from experimental model systems. These have implications for structuring future research and understanding disease and development.

Key points

  • Epigenetics is the study of variations in gene function (phenotypes) that are somatically heritable (and sometimes also from one generation to the next), but which are not caused by genetic alterations.

  • In plants and animals, different epigenetic modifications, including DNA methylation, can have long-term effects on gene expression.

  • The environment affects gene expression and phenotypes, both in plants and animals. Although it triggers natural developmental processes in some species, it often has deleterious effects that have consequences for development and disease.

  • Different environmental cues (such as nutrition, chemical compounds, temperature changes and other stresses) can affect phenotypes and epigenetic gene regulation in experimental model systems.

  • A growing number of human studies have demonstrated long-term effects as a consequence of diet, exposure to chemical components and other external factors. The effects are particularly apparent when exposure to the environmental factor occurs during gestation.

  • For many environmentally induced phenotypes, particularly in humans, it remains unclear to what extent epigenetic modifications could be involved. This is a challenge for future research.

  • Genetic differences between individuals influence epigenetic deregulation, and possibly also susceptibility to environmental stresses.

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Acknowledgements

We thank F. Berger, M. Constância, the reviewers and all members of our teams for helpful comments and discussions. We apologize to our colleagues whose research we were unable to review owing to the focus on selected model systems, and because of space limitations. M.F.F. is grant supported by the Spanish Ministry of Health (PS09/02454) and the 'Obra Social Cajastur'. R.F. acknowledges grant funding from the 'Institut National du Cancer', the 'Ligue Contre le Cancer', the 'Agence Nationale de la Recherche' and the UK Agency for International Cancer Research. He is affiliated to the European network EpiGeneSys.

Author information

Affiliations

  1. Institute of Molecular Genetics (IGMM), CNRS UMR-5535 and the University of Montpellier, 1919 route de Mende, 34293 Montpellier, France.

    • Robert Feil
  2. Department of Immunology and Oncology, Centro Nacional de Biotecnología (CNB-CSIC), Madrid, Spain.

    • Mario F. Fraga
  3. Cancer Epigenetics Laboratory, Institute of Oncology of Asturias (IUOPA-HUCA), University of Oviedo, Spain.

    • Mario F. Fraga

Authors

  1. Search for Robert Feil in:

  2. Search for Mario F. Fraga in:

Competing interests

The authors declare no competing financial interests.

Corresponding author

Correspondence to Robert Feil.

Glossary

Epigenetic modifications

Chemical additions to the DNA and histones that are stably maintained and do not change the primary DNA sequence.

Epigenomes

The overall epigenetic modifications of cells. An organism has multiple, cell type-specific, epigenomes.

Intrinsic factors

Factors that are inherent to the individual animal or plant. Genetically determined, intrinsic factors induce considerable stochastic variation, such as different behaviour between cells.

CpG dinucleotides

Indicates a cytosine followed (5′–3′) by a guanine. Cytosines at CpG dinucleotides constitute the principal target of DNA methylation in mammals. In plants, cytosine methylation occurs also in other sequence contexts.

Heterochromatin

A densely packaged, transcriptionally silenced type of chromatin. Constitutive heterochromatin is found close to centromeres in all tissues. Facultative heterochromatin, such as that commonly found at gene promoters, can be developmentally reprogrammed.

Phenotypic plasticity

The ability of a genotype to yield different phenotypes; for example, in response to environmental stimuli.

Metastable epiallele

An allele for which the expression depends on environmentally influenced, stochastic establishment of epigenetic states during early development.

Imprinted genes

Genes that express one of their two alleles only, in a parent-of-origin-specific manner.

Folate

(Vitamin B9). A water-soluble B vitamin that is abundant in green vegetables and fruits. Folate derivatives are important substrates in many one-carbon-transfer reactions.

Methionine

An essential amino acid that is abundant in fish, eggs and some seeds and vegetables.

CpG islands

GC-rich DNA sequences (of 200–2,000 bp in length) that have a high density of CpG dinucleotides. Approximately half of the mammalian genes have a CpG island near the transcription start site, often with promoter activity.

Vitamin B12

(Cobalamin). A vitamin that is abundant in meat, seafood, eggs and dairy foods. It is a fundamental cofactor in the regeneration of methionine from homocysteine, and in other biochemical reactions.

Endocrine disruptors

Chemical compounds that affect endocrine regulation and cause developmental alterations, cancer and other pathologies.

Polycomb group proteins

A family of chromatin-modifying proteins that are involved in chromatin silencing. They are organized into Polycomb repressive complexes (PRCs) that catalyse histone H3 lysine-27 trimethylation and histone H2A lysine-119 ubiquitination.

Vitamin B6

(Pyridoxal phosphate). A vitamin that is abundant in meat, fish and some tubers and fruits. It is a crucial cofactor in the trans-sulphuration of homocysteine and in other biological reactions.

Betaine

A molecule that is abundant in whole-wheat foods and some green vegetables. Some organisms can synthesize betaine from choline.

Choline

A soluble molecule that is abundant in meat, fish, seafood, eggs, dairy foods and some vegetables, seeds and nuts.

Methyl donor

A chemical compound that can donate a methyl group. The universal methyl donor for DNA methylation and histone methylation is S-adenosylmethionine (SAM).

Butyrate

A short-chain carboxylic acid that is produced by bacteria in the gut as an end product of the fermentation of dietary carbohydrates.

Sirtuins

A family of proteins that couple lysine deacetylation to NAD+.

Bivalent chromatin

Regions of chromatin that have co-occurrence of histone H3 trimethylated on lysine-27 (H3K27me3) and H3K4me2/3 during embryonic development.

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DOI

https://doi.org/10.1038/nrg3142

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