Ridings-Figueroa, Rebeca, Stewart, Emma R., Nesterova, Tatyana B. et al. (14 more authors) (2017) The nuclear matrix protein CIZ1 facilitates localization of Xist RNA to the inactive X-chromosome territory. Genes and Development. pp. 876-888. ISSN 1549-5477
Abstract
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-de-pendent 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.
Metadata
Item Type: | Article |
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Authors/Creators: |
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Copyright, Publisher and Additional Information: | © 2017 Ridings-Figueroa et al. |
Keywords: | CIZ1,Lymphoproliferative disorder,Nuclear matrix,X-chromosome inactivation,Xist,lymphoproliferative disorder,nuclear matrix,Humans,Male,Embryo, Mammalian/metabolism,RNA, Long Noncoding/genetics,X Chromosome/genetics,Fibroblasts/metabolism,Lymphoproliferative Disorders/genetics,Mice, Inbred CBA,Female,Nuclear Proteins/physiology,Cell Differentiation,Mice, Inbred C57BL,Cells, Cultured,Gene Expression Regulation,Sex Characteristics,Embryonic Stem Cells/metabolism,Mice, Knockout,Animals,Mice,X Chromosome Inactivation |
Dates: |
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Institution: | The University of York |
Academic Units: | The University of York > Faculty of Sciences (York) > Biology (York) The University of York > Faculty of Sciences (York) > Chemistry (York) |
Depositing User: | Pure (York) |
Date Deposited: | 25 Apr 2017 10:21 |
Last Modified: | 07 Jan 2025 00:09 |
Published Version: | https://doi.org/10.1101/gad.295907.117 |
Status: | Published |
Refereed: | Yes |
Identification Number: | 10.1101/gad.295907.117 |
Related URLs: | |
Open Archives Initiative ID (OAI ID): | oai:eprints.whiterose.ac.uk:115604 |
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Filename: Genes_Dev._2017_Ridings_Figueroa_876_88.pdf
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Licence: CC-BY-NC 2.5