Mammalian developmental epigenetics
KeywordsEpigenetics, X-chromosome inactivation, Chromatin, Mouse development, Nuclear organization
In female mammals, one of the two X chromosomes is transcriptionally silenced during early development, a process that allows for dosage compensation between XX females and XY males. This process, known as X-chromosome inactivation, is a paradigm for developmental epigenetics.
To analyse the early steps of X-chromosome inactivation we study mouse embryos and mouse embryonic stem cells. In parallel, we also use human cancer cell lines, as well as breast tumor samples in collaboration with doctors at the Curie Hospital, to investigate the mechanisms underlying epigenetic instability in the context of tumor development.
We couple classic molecular approaches with the analysis of cellular behavior at the single-cell level, in fixed or live samples, thanks to the the Institut Curie’s imaging platform and the state-of-the-art microscopy tools and expertise available within the Genetics and Developmental Biology department. These approaches are combined with large-scale genomic and epigenomic techniques made possible thanks to the various technological departments of the Institut Curie. Our work is especially focused on changes in chromatin structure and nuclear organization associated with heterochromatin formation, as well as the role of non-coding RNAs such as the remarkable Xist RNA which is expressed specifically from the inactive X and underlies the initiation of X inactivation.