X chromosome inactivation; linking mechanisms for in cis accumulation of Xist RNA and chromosome silencing
Prof Neil Brockdorff
University of Oxford
Mammals have evolved a process called X-inactivation to ensure that XX females have the same levels of the X chromosome genes as XY males. This is achieved by switching off a single X chromosome during early female embryogenesis. Our previous studies have shown that X-inactivation is orchestrated by an unusual non-coding RNA molecule, called Xist. Xist RNA is expressed from a single X chromosome in female cells and accumulates locally over the entire chromosome territory. Localised Xist RNA recruits factors that silence underlying genes by modifying chromatin structure.
Our goal is to understand the molecular mechanism of X-inactivation. We will investigate key factors required for local accumulation of Xist RNA and Xist-mediated silencing, determining their mode of action. We will apply synthetic biology approaches to demonstrate that the pathways we have identified are able to define Xist function in cells.