Environmental chemical exposures and human epigenetics

Abstract

Every year more than 13 million deaths worldwide are due to environmental pollutants, and approximately 24% of diseases are caused by environmental exposures that might be averted through preventive measures. Rapidly growing evidence has linked environmental pollutants with epigenetic variations, including changes in DNA methylation, histone modifications and microRNAs. Environ mental chemicals and epigenetic changes All of these mechanisms are likely to play important roles in disease aetiology, and their modifications due to environmental pollutants might provide further understanding of disease aetiology, as well as biomarkers reflecting exposures to environmental pollutants and/or predicting the risk of future disease. We summarize the findings on epigenetic alterations related to environmental chemical exposures, and propose mechanisms of action by means of which the exposures may cause such epigenetic changes. We discuss opportunities, challenges and future directions for future epidemiology research in environmental epigenomics. Future investigations are needed to solve methodological and practical challenges, including uncertainties about stability over time of epigenomic changes induced by the environment, tissue specificity of epigenetic alterations, validation of laboratory methods, and adaptation of bioinformatic and biostatistical methods to high-throughput epigenomics. In addition, there are numerous reports of epigenetic modifications arising following exposure to environmental toxicants, but most have not been directly linked to disease endpoints. To complete our discussion, we also briefly summarize the diseases that have been linked to environmental chemicals-related epigenetic changes.

Figure 1

Transcriptional regulation at the epigenetic level. Epigenetic mechanisms, including DNA methylation, histone modifications and miRNAs, regulate chromatin compaction and gene expression. DNA methylation at CpG sites usually suppresses gene expression. Histones are globular proteins that undergo posttranslational modifications, such as Ac, methylation and phosphorylation, thus influencing chromatin structure and gene expression. Active genes are usually characterized by low DNA methylation and highly acetylated chromatin configuration that allow access to transcription factors. miRNAs are a set of small, non-protein-coding RNAs that negatively regulate expression of target genes at the posttranscriptional level by binding to 3′-untranslated regions of target mRNAs