Our group investigates X-chromosome reactivation during the specification of the germline. This female-specific reprogramming pathway is a paradigm of epigenetic resetting and fine gene-regulation control. A better understanding of the mechanisms involved in gene expression regulation and epigenetic memory is crucial, especially in the very unique context of the germ line formation.
Epigenetic memory plays a determinant role in locking cell fates through inheritance of chromatin modifications such as DNA methylation and histone marks. This is paramount for the stability of gene expression programs, cell identity and functions. In mammals, the most drastic transition in cell fate coincides with the emergence of the germline in the embryo. It involves a profound epigenetic remodelling of the cells. Occurring in both sexes, germline reprogramming is essential for the specialization of reproductive cells, and therefore, for the perpetuation of the species. However, in females specifically, reactivation of the entire inactive X chromosome, an epigenetic hallmark of female somatic cells, accompanies the acquisition of germline identity. Incidentally, this leads to a biallelic expression of X-linked gene in the germline precursors of XX females compared to XY males, at the onset of gonadal sex determination. The biological impact and significance of this sex-specific epigenetic characteristics is unknown. However, the presence of a non-reactivated X chromosome could be detrimental to homologous chromosome pairing and segregation in meiosis, and could lead to maternally inherited sex-chromosome aneuploidies such as XO and XXY syndromes in humans.
In the group, we aim to investigate the specificity and principles of female germline epigenetic reprogramming by :
1) Mapping the reshuffling of the epigenetic landscape on the active and inactive X chromosomes and in a sex-specific manner.
Techniques: mouse, cytometry, low-input CUT&RUN, ChIPseq, WGBS
2) Identifying the molecular mechanisms involved in X-chromosome reactivation in a culture-based system of germ cells.
Techniques: cell culture, mPGCLC, cytometry, RNAseq, CRISPR screen
3) Investigating the reciprocal influence between X-chromosome activity and global genome transcription.
Techniques: cell culture, mPGCLC, cell nornalized RNAseq, RNA-FISH
Ultimately, this work will have broader implications for sex-chromosome related infertility and aneuploidy syndromes, stem cell and reproductive medicine, as well as epigenetic inheritance and cancer.