Structure and function of CIZ1/RNA complexes

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X chromosome inactivation (XCI) serves as a model for establishment and maintenance of selective transcriptional silencing throughout the genome. The nuclear matrix 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. CIZ1 is recruited to the inactive X chromosome (Xi) in female cells in a manner dependent on the archetypal long non-coding RNA (LNCRNA) Xist, while retention of Xist at Xi is dependent on CIZ1 in somatic cells, suggesting co-dependency. Recent data argue for a role in maintenance of chromatin state during Xi replication in S phase of the cell cycle. This project will investigate the requirements for and mechanism of retention and release of CIZ1-Xist particles at Xi. It will use a range of molecular, cellular and structural biology techniques, including mammalian cell culture and cell cycle analysis, cell-free reconstitution of regulated events, high resolution imaging, X-ray crystallography and cryo-EM, with scope to develop the project in a number of ways.