Abstract: Series 109, Lecture 2

The Harvey Lectures Series 109 (2013—2014)

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Lecture #2: Thursday, November 21, 2013 — Watch Video of Lecture

X-Chromosome Inactivation: Remembering Silence and Knowing When to Forget

Edith Heard, PhD

Edith Heard, PhD

Professor, Collège de France
Research director 1st class, Centre national de la recherche scientifique
Director, Developmental Biology and Genetics

Curie Institute

Paris, France

Dr Heard's Website

The process of X-chromosome inactivation enables dosage compensation in mammals, and is a striking example of epigenetic regulation that raises several interesting questions. How are identical DNA sequences differentially treated in the same nucleus? How are differential states of gene expression stably propagated over hundreds of cell divisions during development, and yet reprogrammed at specific stages or under certain conditions? My research has focused on this fascinating process for more than two decades: its developmental dynamics, its spatio-temporal regulation, and its underlying molecular mechanisms. Our work in the mouse has shown that X inactivation is highly dynamic during early development, revealing a remarkable epigenetic plasticity in the early embryo, which contrasts with its stability in the soma. We also found that during the initiation of XCI, the X chromosomes display a unique spatial choreography in the nucleus. Transient homologous pairing between the two X chromosomes is observed, just prior to the up-regulation on one X of the non-coding Xist RNA, which is the trigger for chromosome-wide silencing. We and others have shown that Xist RNA coating induces a unique chromatin structure and chromosome conformation, as well as forming a silent nuclear compartment into which genes are recruited as they become inactivated. The multiple functions of the Xist transcript and its complex regulation have rendered it a paradigm for non-coding RNAs.