Institut of Molecular Genetics , Montpellier - UMR5535

 Epigenetic Reprogramming and Development Team

 

In my group, we investigate X-chromosome reactivation during the specification of the germline. This reprogramming pathway is a paradigm of epigenetic resetting and fine gene-regulation control.

 

During my doctoral work (2006-2010) with Luisa Dandolo in the Cochin Institute (Paris, France), I studied the role of the imprinted Igf2/H19 locus during embryogenesis. My main achievement was to reveal that MyoD (master transcription factor for myogenesis), Igf2 and H19 participate in a gene network that is essential for skeletal muscle development and brown adipose tissue.

I then performed a postdoc (2011-2015) on another epigenetic mechanism: X-chromosome inactivation in the laboratory of Edith Heard (Institut Curie, Paris). I aimed at resolving the chromosome-wide dynamics of X-linked gene inactivation in early mouse embryos. For this purpose, I pioneered allele-specific single-cell RNA sequencing and discovered that the absence of X-chromosome inactivation leads to dosage compensation failure and lack of activation of the extra-embryonic lineages at the blastocyst stage. At this stage, the inactive X-chromosome immediately undergoes a reverse process of inactivation in the cells that give rise to the embryo proper - the inner cell mass. Very little was known about this early reactivation phase. Using state-of-the-art in vivo single-cell approaches - allele-specific RNAseq and nascent RNA-FISH - I revealed the temporal and locus-specificity of X-linked gene reactivation.

At the end of my postdoctoral study in the Heard laboratory, I was fascinated by the cycle of X-chromosome inactivation and reactivation in the germline and the early embryo. I then contacted Azim Surani (University of Cambridge, UK), who is a pioneer in the germ cell field, to join his laboratory (2015-2018). I studied the X-linked gene reactivation in female primordial germ cells and showed that X-chromosome reactivation kinetics are very different in mouse germline compared to the inner cell mass of the embryo. My previous studies highlight the fact that X-linked gene reactivation kinetics are intrinsic to the cell state i.e., the pluripotent inner cell mass or the very specific context of the germ cells. This led to my recruitment as a research scientist in the CNRS and opens the path of my actual scientific interest, leading me to raise the following questions: how can the silent state of a gene, fixed at an earlier stage, be revoked? Does an epigenetic memory of the silent state exist and what mechanisms are involved in overriding it? What are the consequences of a defective X-chromosome reprogramming for the formation of the germline and the development of the progeny?

 

To resolve these fundamental questions, the team “Epigenetic Reprogramming and Development” will open at the Institut de Génétique Moléculaire de Montpellier (IGMM, UMR5535), in December 2020 with the support of the FRM Amorçage Jeunes Equipes and the ATIP-AVENIR program.