Functional analysis of CIZ1

We are interested in the structure, function and disease implications of the CIZ1 protein, and related factors involved in organisation of the mammalian cell nucleus. Recent work has focussed on its interaction with Xist long non-coding RNA 1 2, and its role in the maintenance of chromatin modifications at the inactive X chromosome (Xi) 3. This project will continue to exploit Xi as a model system and explore the interaction between CIZ1 and regulatory factors that modulate it’s function in the cell cycle. The goal is to understand the impact of changes in CIZ1 that are common in human cancers 4 5, and to assess the extent to which these destabilise epigenetic state in early stage tumours. Core techniques will be mammalian cell culture and synchronisation, molecular biology techniques to generate expression vectors, immunofluorescence microscopy and quantitative image analysis. Further opportunities exist for transcriptomic analysis or biochemical approaches, depending on interests and the needs of the project.

1. Ridings-Figueroa, R. et al. The nuclear matrix protein CIZ1 facilitates localization of Xist RNA to the inactive X-chromosome territory. Genes Dev 31, 876-888 (2017).
2. Sunwoo, H., Colognori, D., Froberg, J.E., Jeon, Y. & Lee, J.T. Repeat E anchors Xist RNA to the inactive X chromosomal compartment through CDKN1A-interacting protein (CIZ1). Proc Natl Acad Sci U S A 114, 10654-10659 (2017).
3. Stewart, E.R. et al. Maintenance of epigenetic landscape requires CIZ1 and is corrupted in differentiated fibroblasts in long-term culture. Nat Commun 10, 460 (2019).
4. Higgins, G. et al. Variant Ciz1 is a circulating biomarker for early-stage lung cancer. Proc Natl Acad Sci U S A 109, E3128-3135 (2012).
5. Rahman, F.A., Aziz, N. & Coverley, D. Differential detection of alternatively spliced variants of Ciz1 in normal and cancer cells using a custom exon-junction microarray. BMC Cancer 10, 482 (2010).