The CompleX Story of How and Why to Turn a Chromosome OFF and ON Again
Centre for Genomic Regulation (CRG) Barcelona
The mammalian germline undergoes extensive epigenetic reprogramming during the development of eggs and sperm. Specifically, the epigenome must be reset before parental marks can be established and passed on to the next generation. In the female germline, X-chromosome inactivation and reactivation represent significant epigenetic reprogramming events, yet our understanding of their kinetics and biological significance remains limited.
Here I will present or recent work on the mechanisms and biological roles of X-inactivation and –reactivation in the context of induced pluripotency and during in vitro mouse germ cell development. In the first story we conducted a genome-wide CRISPR-screen to identify pathways crucial for reprogramming and the associated X-reactivation process. Our findings revealed that Interferon-gamma signaling acts as an enhancer of X-reactivation efficiency and reprogramming speed.
In the second part of my talk, we investigated the dynamics of X-inactivation and reactivation using an in vitro system of primordial germ cell-like cell (PGCLC) differentiation. We found a fine-tuned sequence of X-chromosome inactivation and reactivation to be a critical feature of female germ cell development. We now possess direct evidence that normal X-chromosome dynamics is not only a diagnostic mark, but also functionally vital for PGCLC differentiation, efficient meiosis and oogenesis.