Edith Heard

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

Professor Edith Heard obtained her PhD from the Imperial Cancer Research Fund (later Cancer Research UK), London. Thereafter, she spent nine years at the Institut Pasteur in Paris, before undertaking a one-year sabbatical at Cold Spring Harbor in the USA. In 2001, she set up her group at the Institut Curie and in 2010 became Director of the Institute’s Genetics and Developmental Biology Unit. Edith was appointed as a Professor of the Collège de France in 2012, holding the Chair of Epigenetics and Cellular Memory. In January 2019, Edith started as Director General of EMBL.

Edith’s group was among the first to show that the epigenetic process of X-chromosome inactivation (XCI), whereby one of a female’s two X chromosomes is silenced during development, is remarkably dynamic. In collaboration with Job Dekker, Edith’s group was also one of the first to describe topologically associating domains (TADs) – a new principle of chromosome folding whereby regions of DNA preferentially interact with each other to partition the genome into functionally distinct domains. Edith’s group showed that this organisation is crucial for the initiation of XCI, as well as being intimately linked to gene expression dynamics. Edith’s current research focuses on understanding how chromatin and chromosome organisation participate in gene regulation.

Edith and her laboratory have been recognised by many prizes, most recently the Hansen Family Award, Inserm Grand Prix, the European Society for Human Genetics Award and the Prix René et Andrée Duquesne of la Ligue contre le cancer. Edith is an Honorary Fellow of Emmanuel College, at the University of Cambridge, a Fellow of the Royal Society and an EMBO member. Edith has participated in numerous scientific boards and is currently a member of the
Scientific Advisory Board of the CNRS (France), the BRIC (Copenhagen, Denmark), the IMBB (Crete, Greece) and the Crick Institute (London, UK).

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

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.