Edith Heard

Mammalian developmental epigenetics

Edith Heard

Development & Epigenesis We are interested in understanding the mechanisms underlying the early steps and the maintenance of X inactivation during mammalian development.

Epigenetics We are interested in the nature and the timing of all the epigenetic changes that accompany X inactivation during development and differentiation.

Stem cells and Life time potential We use mouse embryonic stem (ES) cells as a model to study the establishment of X-chromosome inactivation, as well as Epiblast stem (EpiSC) cells and neural progenitor cells (NPCs) to analyze downstream events.

In female mammals one of the two X chromosomes is silenced during early development to enable dosage compensation for X-linked gene expression between the sexes. The inactive state is maintained stably through cell divisions but can also be reversed, for example in the germ line. X-chromosome inactivation (XCI) represents one of the most striking examples of epigenetics in mammals, as a heritable change in gene expression is induced by a non-coding RNA (Xist), and is maintained thanks to chromatin changes and spatio-temporal segregation. XCI is also a classic example of facultative heterochromatin, as one whole X chromosome is present in a silent condensed state within the same nucleus as its active counterpart.

My lab focuses on the XCI process in order to gain general insights into epigenetic regulation during normal development, as well as in diseases such as cancer. Our goal has been to decipher mechanisms of gene expression and epigenetic regulation in XCI at multiple timescales: over the cell cycle, during development and in adult life, using molecular, cellular and genetic approaches. Studying this process has allowed us to make several insights into gene regulation, chromatin, nuclear organization and chromosome structure, notably the discovery of topologically associated domains (TADs) spanning several hundred kilobases, within which genes and their regulatory sequences preferentially interact.

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