Role of CIZ1 in X chromosome inactivation

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X chromosome inactivation (XCI) serves as a model for establishment and maintenance of selective transcriptional silencing throughout the genome,through the action of polycomb repressive complexes (PRC) 1 and 2. The nuclear matrix (NM) protein Cip1-interacting zinc finger protein 1 (CIZ1) plays a role in DNA replication in association with cyclins, and is linked with adult and paediatric cancers. We recently showed that CIZ1 is located at the Xi in mouse and human female cells, and that absence of CIZ1 leads to highly penetrant female-specific lympho-proliferative disorder. The data argue for a role in maintenance of X chromosome inactivation through association with the nuclear matrix. This project will investigate the mechanism by which CIZ1 functions in the maintenance of epigenetic marks as cells pass through the cell cycle, and will use a range of molecular and cellular biology techniques including high resolution and live imaging.