The activity of our genes is determined by more than their DNA sequence alone. Active and silent genes are distinguished by ‘epigenetic’ marks – chemical tags that are added to the DNA or to the proteins around which the DNA is organised on chromosomes. Such epigenetic differences can be very stable, reinforcing and perpetuating decisions normally made very early during the development of different tissues, such that each tissue in our body has a distinct ‘epigenome’ – the sum of all the epigenetic marks on the DNA of a single cell.
The erosion of epigenetic marks may occur during ageing and contribute to some diseases, such as cancer. But our epigenetic history may even begin before conception. Our gametes – the sperm and egg – have very distinct epigenomes, but while much of the epigenetic information inherited from the sperm and egg is erased soon after fertilisation, some remains throughout our lives. This epigenetic memory of our parents occurs naturally in a class of genes call imprinted genes, but it is also possible that epigenetic mistakes can arise in the sperm, egg or early embryo and persist during development and cause disease in later life or in future generations.
Until recently, the epigenetic landscape of our gametes was unknown. Advances in sequencing and the ability to profile epigenetic marks in very small numbers of cells – and even in single cells – have enabled us to generate detailed epigenomic maps of the egg, sperm and embryo and to investigate the processes responsible for normal epigenetic marking (Hanna, Demond and Kelsey 2018). These new methods are helping to reveal how epigenetic errors may arise in gametes and early embryos – owing to poor nutrition, exposure to environmental pollutants, genetic causes, or associated with infertility.