The nuclear matrix protein CIZ1 facilitates localization of Xist RNA to the inactive X-chromosome territory

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Author(s)

  • Rebeca Ridings-Figueroa
  • Emma R. Stewart
  • Tatyana B. Nesterova
  • Heather Coker
  • Greta Pintacuda
  • Jonathan Godwin
  • Rose Wilson
  • Aidan Haslam
  • Fred Lilley
  • Renate Ruigrok
  • Sumia A. Bageghni
  • Ghadeer Albadrani
  • William Mansfield
  • Jo-An Roulson
  • Neil Brockdorff
  • Justin F. X. Ainscough
  • Dawn Alison Coverley

Department/unit(s)

Publication details

JournalGenes & development
DateAccepted/In press - 20 Apr 2017
DateE-pub ahead of print - 25 May 2017
DatePublished (current) - 25 May 2017
Issue number9
Volume31
Number of pages13
Pages (from-to)876-888
Early online date25/05/17
Original languageEnglish

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.

Bibliographical note

© 2017 Ridings-Figueroa et al.

    Research areas

  • CIZ1, Lymphoproliferative disorder, Nuclear matrix, X-chromosome inactivation, Xist

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