The importance of gene dosage in development and disease: unravelling the epigenetic process of X-chromosome inactivation in females

Abstract 

Ensuring the right balance of proteins and nucleic acids in the cells of an organism is essential for life. In many organisms, males and females differ thanks to their sex chromosomes and this can lead to major imbalances in gene dosage. In mammals, males have one X and one Y chromosome, while females have two X chromosomes. To achieve dosage compensation, one of the two X chromosomes is converted from the active euchromatic state into inactive heterochromatin during early female development. This classic epigenetic process, known as X-chromosome inactivation, results in the transcriptional silencing of over a thousand X-linked genes. However, some genes are able to escape this process and this can vary between cell types and between individuals. We are interested in the mechanisms that bring about the differential treatment of the two X chromosomes and the epigenetic mechanisms that maintain this inactive state for most genes, as well as those that enable expression and increased dosage for others. Our recent work has uncovered the developmental dynamics of this process and the mechanisms involved in gene silencing. We have also provided insights into X-chromosome organization and its relationship to gene silencing or escape. These findings have implications for our understanding of gene regulation and the importance of correct dosage in development and in disease.  

About the lecture series:

The Bridget Ogilvie Lecture is named after Dame Bridget Ogilvie who was Director of the Wellcome Trust 1991 – 1998 and who played an important role in the development of the College of Life Sciences, in particular in the special award of £10 million that lead to the building of the Wellcome Trust Building in 1997.  Each Wellcome funded Division in SLS takes turns in nominating the Bridget Ogilvie Lecturer and this year is the turn of GRE.