Mechanisms of epigenetic gene silencing caused by the long non-coding Kcnq1ot1 RNA - a key regulator of BWS

Imprinted genes are those genes only expressed (copied into RNA) from one of the parental chromosomes. These genes have important roles in embryonic development, growth, and human diseases including cancer. Imprinted genes occur in clusters in the genome, and some clusters are regulated by long non-coding RNAs (RNA which does not code for proteins), which somehow inactivate the genes located next to them in the cluster. This project will investigate the mechanisms by which the non-coding RNA Kcnq1ot1, deregulation of which underlies the human overgrowth and cancer syndrome Beckwith-Wiedemann syndrome, regulates gene silencing. This will include investigations of physical interactions of the RNA with the gene cluster, and the consequent change of higher order organisation of the gene cluster.