The activity of our genes is determined by more than just the sequence of DNA. Epigenetic marks are reversible chemical modifications to our DNA or chromatin that alter the activity of the genes upon which they sit.
The sum of epigenetic marks in a tissue is known as the epigenome. These modifications play important roles in defining different cell types in the body and can be influenced by environmental and nutritional factors. It is known that epigenetic marks decline during the ageing process.
All cells in the body are derived from stem cells, which have the unique ability of being able to give rise to any cell type. We are particularly interested in the epigenomes of the stem cells that contribute to, and are present in, the early embryo. Using these cells we can uncover how the epigenome is regulated throughout life, from before the point of conception, and how it is affected by ageing.
Unravelling the epigenome
Using state-of-the-art technology, most of which we have developed ourselves, we are performing highthroughput analyses to study the epigenome and gene expression patterns of mammals during embryonic development. We are looking at multiple cell types including germ cells (which beget eggs and sperm), zygotes (fertilised eggs) and newly formed embryos. Together, this information allows us to unravel how epigenetic marks influence development. These data will be made available through online resources, providing useful datasets to national and international researchers. The cells that form the placenta and the developing embryo are specified during very early development. We are defining the epigenome of the placental cells and uncovering the pathways that set these apart from embryonic cells.
In most cell types, epigenetic marks are maintained during cell division and are important for continued cell identity. In the case of the germ cells, and the newly formed zygote, historic marks are unnecessary since these cells form the basis of new life and must be able to develop into all specialised cell types. Here a process called reprogramming removes the existing marks and the epigenome is reset. However, this resetting is not always complete, leading to the possibility that epigenetic marks might be inherited from grandparents to parents to children. As well as looking at the epigenome in young cells that are dividing and actively maintaining their epigenetic marks, we study long-lived cells that do not divide – the cardiac myocytes in the heart. Comparison of young and old heart tissue will demonstrate how the epigenome declines during ageing.
Regulating the epigenome
We are defining signalling pathways in stem cells that induce reprogramming of the epigenome on a large scale. Additionally, we are studying the enzymes that regulate the epigenome together with factors such as RNA that can help to target specific epigenetic marks. Eventually this will provide approaches by which epigenetics can be manipulated in cells and organisms, potentially leading to enhanced stem cells (epigenetic rejuvenation), and applications in regenerative medicine.