Journal
GENES & DEVELOPMENT
Volume 31, Issue 9, Pages 876-888Publisher
COLD SPRING HARBOR LAB PRESS, PUBLICATIONS DEPT
DOI: 10.1101/gad.295907.117
Keywords
CIZ1; Xist; X-chromosome inactivation; nuclear matrix; lymphoproliferative disorder
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Funding
- Radhika Sreedhar Scholarship
- University of York priming funds
- Biotechnology and Biological Sciences Research Council PhD training scholarships
- Genetics Society training funds
- Wellcome Trust [081385, 091911]
- Micron Advance Imaging Initiative (Wellcome Trust) [103768]
- Biotechnology and Biological Sciences Research Council [1643825] Funding Source: researchfish
- Wellcome Trust [103768/Z/14/Z] Funding Source: researchfish
- BBSRC [1643825] Funding Source: UKRI
- Wellcome Trust [103768/Z/14/Z] Funding Source: Wellcome Trust
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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.
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