Dr Gavin Kelsey

As well as genetic information, the egg and sperm also contribute epigenetic annotations that may influence gene activity after fertilisation. These annotations may be direct modifications of the DNA bases or of the proteins around which the DNA is wrapped into chromatin. Such epigenetic marking is a normal mechanism by which genes are controlled, but epigenetic information can also be modified by environmental factors. Our goal is to understand whether, through epigenetics, factors such as a mother’s age or diet have consequences on the health of a child.

We examine how epigenetic states are set up in oocytes – or egg cells – and influence gene expression in the embryo. We have shown that DNA methylation – the direct epigenetic modification in DNA – is patterned in oocytes in response to gene transcription, including at imprinted genes. This demonstrates the principle that where genes are transcribed in oocytes can determine how they are expressed in offspring. This link could provide a logic for how maternal physiological or pathological states could cause altered methylation patterning. It is also shown that repressive chromatin marks in oocytes can lead to long-term silencing of genes inherited from the mother, particularly in cells that will form the placenta. We are particularly interested in the genetic elements that transmit this inherited gene silencing.

To investigate these questions, we develop methods to profile epigenetic information in very small numbers of cells or even in single cells.