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

Emma R. Stewart, Robert M. L. Turner, Katherine Newling, Rebeca Ridings-Figueroa, Victoria Scott, Peter D. Ashton, Justin F. X. Ainscough and Dawn Coverley ()
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Emma R. Stewart: University of York
Robert M. L. Turner: University of York
Katherine Newling: University of York
Rebeca Ridings-Figueroa: University of York
Victoria Scott: University of York
Peter D. Ashton: University of York
Justin F. X. Ainscough: University of York
Dawn Coverley: University of York

Nature Communications, 2019, vol. 10, issue 1, 1-13

Abstract: 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.

Date: 2019
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DOI: 10.1038/s41467-018-08072-2

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