In the Lee lab, I will investigate molecular interactions that govern the silencing of the X chromosome. Female mammals possess two X chromosomes; early in development, one of those chromosomes gets almost completely silenced. This inactivation allows for gene activity in female cells to remain at levels equivalent to those found in male cells, which have only one X chromosome, and it involves coating the entire chromosome with repressive factors that direct it to become tightly condensed. Before this condensation can take place, some enzymes and cofactors that modify chromatin must remove chromosomal marks that favor leaving the X chromosome in a looser, more open configuration. Using state-of-the-art techniques in cell and molecular genetics and super-resolution microscopy, I will determine how these enzymes cooperate with the canonical factors that drive repression—and how these interactions are coordinated in female cells by a molecule called Xist, the master regulator of X inactivation. I will also examine how disrupting the activity of these components alters the silencing process, findings that could lead to novel therapies for reactivating genes in disorders linked to the X chromosome, such as Rett and Fragile X syndromes.