Epigenetics and DOHaD: from basics to birth and beyond

* Address for correspondence: T. Bianco-Miotto, School of Agriculture, Food and Wine, Waite Research Institute & Robinson Research Institute, University of Adelaide, SA, 5005, Australia. (Email [email protected])

Epigenetic mechanisms

There are numerous definitions of epigenetics including the study of modifications such as DNA methylation, histone modifications and non-coding RNAs, which result in altered gene regulation without changing the underlying DNA sequence. These modifications alter gene expression by altering the genome architecture and accessibility. The term ‘epigenetics’ was first coined in 1942 by Conrad Waddington. ¹ As a developmental biologist, he coined the term to explain how different cell types arose throughout development from the one genome. ¹ In other words, epigenetics was how one genotype could give rise to the different phenotypes. ¹

There are many examples of epigenetic modifications that impact on phenotype. One of these is the Agouti mouse model where epigenetic regulation of the Agouti viable yellow (A ^vy ) allele determines coat colour and predisposition to obesity and disease. ² When the A ^vy allele is expressed, the mice have a yellow coat colour and are obese and more susceptible to developing diabetes and cancer. However, when female Agouti mice are fed a high methyl supplemented diet (folic acid, vitamin B₁₂, choline, betaine) their offspring are brown in colour and healthy and this is associated with increased DNA methylation and silencing of A ^vy . ³ The Agouti mouse has been a widely used model to show how the environment can impact epigenetics and hence phenotype.

Another example of an epigenetic phenomenon is monozygotic (identical) twins who do not share disease phenotypes, potentially due to their different environmental exposures resulting in changes in their epigenome. ^4,5 Hence, an alternative definition for epigenetics are the mechanisms that result in phenotypic trait differences caused by environmental factors that impact on gene regulation.

Epigenetic modifications

Epigenetic modifications include DNA methylation, histone modifications and non-coding RNAs. Each of these epigenetic modifications can impact gene expression, however they are not independent of each other. ⁶ DNA methylation is the addition of a methyl group to a cytosine, predominantly in the context of a CpG but non-CpG DNA methylation is also an important regulator of gene expression. ⁷ DNA methylation at...