Cancelled

Part of the Mendel at 200 conference

Abstract: In female mammals, one of the two X chromosomes becomes inactivated during early development in order to achieve X-chromosome dosage compensation between the sexes. X-chromosome inactivation (XCI) is usually initiated at random in eutherian mammals and the choice of inactive X is then stably propagated in somatic tissues, leading to clonal populations of cells expressing either the maternal or the paternal X. Thus females are cellular mosaics for X-linked allelic gene expression and this can lead to phenotypic variation both within and between individuals. There is also an increasing realization that the inactive X chromosome contributes to male-female differences in physiology and disease. Indeed, a significant proportion of X-linked genes can escape XCI and the increased dosage of proteins encoded by these genes can lead to genome-wide differences, influencing a wide variety of processes including cell differentiation and metabolism. My lab is interested in understanding how X-chromosome inactivation (XCI) is established and maintained, and how some genes escape XCI mainly using mouse as a model. Establishment of XCI involves the non-coding Xist RNA that coats the chromosome it is expressed from and triggers gene silencing as well as chromatin changes and 3D re-organisation of the X. Our recent work has focused on the role of Xist RNA’s partners in mediating these changes, in particular the SPEN protein, which acts as a platform for multiple factors acting on transcription, chromatin and RNA metabolism. Although most X-linked genes are sensitive to Xist RNA and SPEN in mouse XCI, different genes along the X show very different timing and extent of gene silencing and we are exploring the genetic and epigenetic basis for this differential gene silencing. This should provide important insights into precise mechanisms of transcriptional repression. We are also interested in understanding how some genes along the X chromosome display varying extents of escape from XCI and how this may be linked to sex-biased disorders. Our recent work exploring the process of XCI and the implications of variable expression from the inactive X chromosome will be presented. 

Biography: 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 she 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. Since January 2019, Edith has been Director General of EMBL.

Edith’s laboratory focuses on understanding how chromatin and chromosome organisation participate in gene regulation in development and disease. Her 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. Her lab has worked out many of the molecular mechanisms underlying X-chromosome inactivation and she uses this model to explore fundamental principles of gene regulation, chromatin and epigenetic processes in general. Edith’s group was one of the first to uncover the epigenetic dynamics of XCI during mammalian development and they have provided insights into the regulation and molecular action of the Xist non-coding RNA that triggers XCI.  

Edith and her laboratory have been recognised by many prizes, most recently the L’Oréal-UNESCO For Women in Science International Award and she is a Fellow of the Royal Society, an EMBO Member, and a Foreign Associate member of the National Academy of Sciences (US), an International Member of the National Academy of Medicine (US), a Member of the German National Academy of Sciences Leopoldina, a Corresponding Member of the Royal Academy in Denmark, an Elected Member of Académie des Sciences, Institut de France, and she has an Honorary Degree Doctor of Science Honoris causa at the University of Cambridge, an Honorary Professor Degree at the University of Heidelberg and an Honorary Doctor Degree at the University of Uppsala.

Edith has participated in numerous scientific boards and is currently a member of the Scientific Advisory Board of the Crick Institute (London, UK), Institute Curie (Paris, France), the Howard Hughes Medical Institute (USA), and the WHO Science Council.

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