Areas of Interest
X chromosome inactivation is the epigenetic process by which female mammals achieve gene dosage compensation between XX females and XY males. In mice, there are two forms of X-inactivation: imprinted X-inactivation, in which only the paternal X is inactivated; and random X-inactivation, in which either the paternal or the maternal X gets inactivated. X-inactivation is modulated by the lncRNA Xist (X-inactive specific transcript), which is expressed from and coats the inactive X, acting in cis to recruit repressive complexes. One such complex is the Polycomb Repressive Complex 2 (PRC2). PRC2 catalyzes trimethylation of lysine 27 at histone 3 (H3K27me3), a histone mark associated with gene repression and enriched at the inactive X. Together with EZH1/2 and SUZ12, EED is part of the core complex of PRC2. Previous work from the Kalantry lab suggests that EED might have a PRC2-independent role in the maintenance of epigenetic silencing at the inactive X and a lineage-specific role modulating Xist expression, as deleting Eed, but not Ezh2/1, in mouse stem cells leads to defects in the maintenance of X-chromosome inactivation and Xist expression differs depending on the cell lineage where EED is ablated. My goal is to elucidate the PRC2-independent, lineage-specific role of EED in the context of X chromosome inactivation in mouse extraembryonic stem cells, which have undergone imprinted X-inactivation. This research will give insight into mechanisms of non-genetic inheritance by imprinted gene silencing that occurs in imprinted X-inactivation in mouse extraembryonic stem cell lineages.