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Maintenance of epigenetic landscape requires CIZ1 and is corrupted in differentiated fibroblasts in long-term culture

Author

Listed:
  • Emma R. Stewart

    (University of York)

  • Robert M. L. Turner

    (University of York)

  • Katherine Newling

    (University of York)

  • Rebeca Ridings-Figueroa

    (University of York
    University of Cambridge)

  • Victoria Scott

    (University of York)

  • Peter D. Ashton

    (University of York)

  • Justin F. X. Ainscough

    (University of York)

  • Dawn Coverley

    (University of York)

Abstract

The inactive X chromosome (Xi) serves as a model for establishment and maintenance of repressed chromatin and the function of polycomb repressive complexes (PRC1/2). Here we show that Xi transiently relocates from the nuclear periphery towards the interior during its replication, in a process dependent on CIZ1. Compromised relocation of Xi in CIZ1-null primary mouse embryonic fibroblasts is accompanied by loss of PRC-mediated H2AK119Ub1 and H3K27me3, increased solubility of PRC2 catalytic subunit EZH2, and genome-wide deregulation of polycomb-regulated genes. Xi position in S phase is also corrupted in cells adapted to long-term culture (WT or CIZ1-null), and also accompanied by specific changes in EZH2 and its targets. The data are consistent with the idea that chromatin relocation during S phase contributes to maintenance of epigenetic landscape in primary cells, and that elevated soluble EZH2 is part of an error-prone mechanism by which modifying enzyme meets template when chromatin relocation is compromised.

Suggested Citation

  • Emma R. Stewart & Robert M. L. Turner & Katherine Newling & Rebeca Ridings-Figueroa & Victoria Scott & Peter D. Ashton & Justin F. X. Ainscough & Dawn Coverley, 2019. "Maintenance of epigenetic landscape requires CIZ1 and is corrupted in differentiated fibroblasts in long-term culture," Nature Communications, Nature, vol. 10(1), pages 1-13, December.
    • Handle: RePEc:nat:natcom:v:10:y:2019:i:1:d:10.1038_s41467-018-08072-2
    DOI: 10.1038/s41467-018-08072-2
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