Role of nuclear matrix protein CIZ1 in X chromosome inactivation

X chromosome inactivation (XCI) is a gene dosage compensation mechanism that results in transcriptional silencing of one of the two X chromosomes in female cells. Nuclear matrix protein CIZ1, which has established links with diseases such as cancer, plays a role in initiation of mammalian DNA replication through interaction with cyclin-dependent kinases. Recently it has also been observed to localize to the inactive X chromosome and loss of the protein results in disruption of the long non-coding RNA Xist. In mice, loss of CIZ1 leads to development of a lymphoma-like phenotype in female mice. My project has used RNAseq analysis, immune-detection techniques, and transfections to investigate the relationship between CIZ1 and X inactivation. I present evidence that implicates the C-terminus end of CIZ1 in binding at the Xi region and the N-terminus in recruitment of the protein to the Xi. I have also shown that loss of CIZ1 leads to disruption of the H3K27me3 at the Xi. At the gene expression level, absence of CIZ1 does not lead to any evident gene reactivation from the inactive X or changes in expression of genes at the X inactivation centre (Xic). However, whole-genome analysis showed that loss of CIZ1 causes widespread changes in gene expression, which could underlie the lymphoma-like phenotype in female mice, and begins to suggest a mechanism of action for CIZ1.