DNA methylation at the crossroads of gene and environment interactions

Pui Pik Law, Michelle L. Holland*

*Corresponding author for this work

Research output: Contribution to journalReview articlepeer-review

79 Citations (Scopus)
146 Downloads (Pure)


DNA methylation is an epigenetic mark involved in regulating genome function and is critical for normal development in mammals. It has been observed that the developmental environment can lead to permanent changes in gene expression and DNA methylation, at least at ‘metastable epialleles’. These are defined as regions of the genome that show a variable epigenetic state that is established early in development and maintained through subsequent cell divisions. However, the majority of the known genome does not behave in this manner. Here, we use the developmental origins of adult disease hypothesis to understand environmental epigenomics. Some challenges to studying how DNA methylation is influenced by the environment include identifying DNA methylation changes associated with an environmental exposure in tissues with a complex cellular composition and at genomic regions for which DNA methylation is dynamically regulated in a cell-type specific manner. We also offer a perspective of how emerging technologies may be useful for dissecting the functional contribution of exposure-associated epigenetic changes and highlight recent evidence that suggests that genomic regions that are absent from genome assemblies may be unappreciated hotspots for environmental modulation of the epigenetic state.
Original languageEnglish
Pages (from-to)717-726
Number of pages10
JournalEssays in Biochemistry
Issue number6
Early online date29 Nov 2019
Publication statusPublished - Dec 2019


  • DNA methylation
  • Developmental programming
  • Gene-environment interactions


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