The nuclear matrix protein CIZ1 facilitates localization of Xist RNA to the inactive X-chromosome territory
| Autor: | Ridings-Figueroa, Rebeca, Stewart, Emma R., Nesterova, Tatyana B., Coker, Heather, Pintacuda, Greta, Godwin, Jonathan, Wilson, Rose, Haslam, Aidan, Lilley, Fred, Ruigrok, Renate, Bageghni, Sumia A., Albadrani, Ghadeer, Mansfield, William, Roulson, Jo-An, Brockdorff, Neil, Ainscough, Justin F. X., Coverley, Dawn Alison |
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| Jazyk: | angličtina |
| Rok vydání: | 2017 |
| Předmět: |
Male
Mice Knockout Sex Characteristics X Chromosome Nuclear Proteins Cell Differentiation Fibroblasts Embryo Mammalian Lymphoproliferative Disorders Mice Inbred C57BL Mice Gene Expression Regulation X Chromosome Inactivation Mice Inbred CBA Animals Humans Female RNA Long Noncoding Cells Cultured Embryonic Stem Cells Research Paper |
| ISSN: | 0890-9369 1549-5477 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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