Structure and function of Xist RNA
Xist RNA induces dynamic chromosome-wide epigenetic modifications and conformational changes of the inactive X-chromosome. Xist has unique repeat elements (A-F), which are well conserved among eutherian mammals, emphasizing the importance of Xist repeat elements in X-inactivation. However, except for repeat A, their roles in X-chromosome inactivation have not been explored until recently. The Xist repeat A has been the most intensively studied Xist repeat element and is essential for initial X-linked gene silencing through histone deacetylation. However, our recent studies indicate that other Xist regions and repeat elements have distinct and unique roles in X-linked gene silencing. We seek to define the functional elements across the Xist RNA.
Dynamics of epigenetic modifications and chromatin organization during X-chromosome inactivation
Xist RNA functions as a binding platform for various chromatin factors and chromatin modifying enzymes, including the polycomb repressive complex and nuclear matrix-associated proteins, to facilitate heterochromatinization of the inactive X-chromosome. Our recent studies have implicated that multiple Xist repeat elements and regions interact with various chromatin modifying enzymes and chromatin factors and have a distinct role for X-inactivation. We are interested in defining the cooperative interaction among chromatin factors/chromatin modifying enzymes to establish the unique epigenetic landscape, chromosomal organization, and gene expression profiles of the inactive X-chromosome.