DNA methylation: Small epigenetic changes may have serious health effects

2016 - 11 - 22

DNA methylation: Small epigenetic changes may have serious health effects

The “Immune Endocrine and Epigenetics” research group at LIH’s Department of Infection and Immunity published a review that summaries our current knowledge on the influence of DNA methylation, a frequent epigenetic modification, on phenotype and in particular on disease.

Whereas the human genome is largely static, the epigenome can be dynamically altered by environmental conditions leading to different phenotypes. DNA methylation, which consists of the binding of a methyl group to the DNA base cytosine in cytosine-phosphate-guanine dinucleotides (CpG), is an intensely studied epigenetic change.

Very abundant methylation or complete demethylation can regulate the expression of genes by either silencing or activating them. This on/off switch mechanism is known for many years and is observed in malignant diseases such as cancer. More recently, it has become apparent that DNA methylation can also be fine-tuned, but the biological relevance of subtle DNA methylation is not proven yet.

The review, first-authored by PhD candidate Fleur Leenen, appeared in the open access journal Clinical Epigenetics in September 2016. It reports on the current pathophysiological and clinical associations of small DNA methylation changes and presents a number of studies indicating that those epigenetic alterations can have an influence on the development of non-malignant diseases such as behavioural disorders, cardiometabolic diseases or asthma. The methylation changes may happen very early in childhood following stressful or traumatic experiences, and even already in utero as a result of maternal diet or mood.

‘Though it is difficult to link small DNA methylation changes to specific phenotypes, there is growing evidence that they could be biologically meaningful’, tells Dr Jonathan Turner, last author of the review.

The authors present the example of the glucocorticoid receptor on which they have worked for many years, building up an international reputation. This receptor plays a key role in how we respond to stress, and the development of stress related diseases. Perhaps more importantly, it has a well-characterised transcriptional and translational variability and is thus a very good model to analyse the association between subtle methylation changes and pathology at the single gene level. They also give advice on how epigenome-wide association studies could be improved and interpreted to identify meaningful DNA methylation changes.

Link to publication: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5012062/