Evolutionary epigenetics of X-chromosome inactivation

Female and male mammals are genetically similar, with the exception of their sex chromosomes: females have two X chromosomes (XX) while males have one (XY). To correct this imbalance, X-chromosome inactivation silences one of the two X chromosomes in females. X-inactivation is mediated by "epigenetic" changes, which modify the DNA and its associated proteins. However, the mechanisms regulating this process are poorly understood. In this proposal, we will characterise the process of X-inactivation in marsupials, a mammal that is distantly related to the more common, "placental" mammals. Our findings will identify mechanisms that are conserved, and therefore especially important for X-inactivation, and will provide insight into embryo development, regenerative medicine and infertility. We will also perform genetic modification in marsupials for the first time. Marsupials are an excellent system for studying cancer, immunity and spinal cord regeneration, so our experiments will speed up experimental progress in these other research areas.