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The nuclear matrix protein Cip1-interacting zinc finger protein 1 (CIZ1) promotes DNA replication in association with cyclins and has been linked to adult and pediatric cancers. Here we show that CIZ1 is highly enriched on the inactive X chromosome (Xi) in mouse and human female cells and is retained by interaction with the RNA-dependent nuclear matrix. CIZ1 is recruited to Xi in response to expression of X inactive-specific transcript (Xist) RNA during the earliest stages of X inactivation in embryonic stem cells and is dependent on the C-terminal nuclear matrix anchor domain of CIZ1 and the E repeats of Xist CIZ1-null mice, although viable, display fully penetrant female-specific lymphoproliferative disorder. Interestingly, in mouse embryonic fibroblast cells derived from CIZ1-null embryos, Xist RNA localization is disrupted, being highly dispersed through the nucleoplasm rather than focal. Focal localization is reinstated following re-expression of CIZ1. Focal localization of Xist RNA is also disrupted in activated B and T cells isolated from CIZ1-null animals, suggesting a possible explanation for female-specific lymphoproliferative disorder. Together, these findings suggest that CIZ1 has an essential role in anchoring Xist to the nuclear matrix in specific somatic lineages.

Original publication




Journal article


Genes Dev

Publication Date





876 - 888


CIZ1, X-chromosome inactivation, Xist, lymphoproliferative disorder, nuclear matrix, Animals, Cell Differentiation, Cells, Cultured, Embryo, Mammalian, Embryonic Stem Cells, Female, Fibroblasts, Gene Expression Regulation, Humans, Lymphoproliferative Disorders, Male, Mice, Mice, Inbred C57BL, Mice, Inbred CBA, Mice, Knockout, Nuclear Proteins, RNA, Long Noncoding, Sex Characteristics, X Chromosome, X Chromosome Inactivation