X chromosome inactivation : spreading of silencing

Although considerable advances have been made in XCI research, many questions remain unsolved. The growing list of XCI activators and inhibitors is not complete yet. The mechanisms that direct Xist-mediated gene silencing still need to be resolved, and the cues that ensure the developmental regulation of XCI and its irreversibility upon differentiation await identification. Furthermore, whether the XCI key regulatory factors identified in mouse are conserved across different mammalian species has not yet been addressed, and how escaping genes resist chromosome-wide inactivation also remains a mistery.

In this thesis, we set out to explore different levels of Xist regulation and Xist RNA function in a specific developmental context. Our experimental stategies are based on the generation of genetically modified mouse ES cells.