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

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 depend...

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Autores principales: Stewart, Emma R., Turner, Robert M. L., Newling, Katherine, Ridings-Figueroa, Rebeca, Scott, Victoria, Ashton, Peter D., Ainscough, Justin F. X., Coverley, Dawn
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Nature Publishing Group UK 2019
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6484225/
https://www.ncbi.nlm.nih.gov/pubmed/30692537
http://dx.doi.org/10.1038/s41467-018-08072-2
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author Stewart, Emma R.
Turner, Robert M. L.
Newling, Katherine
Ridings-Figueroa, Rebeca
Scott, Victoria
Ashton, Peter D.
Ainscough, Justin F. X.
Coverley, Dawn
author_facet Stewart, Emma R.
Turner, Robert M. L.
Newling, Katherine
Ridings-Figueroa, Rebeca
Scott, Victoria
Ashton, Peter D.
Ainscough, Justin F. X.
Coverley, Dawn
author_sort Stewart, Emma R.
collection PubMed
description 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.
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spelling pubmed-64842252019-04-29 Maintenance of epigenetic landscape requires CIZ1 and is corrupted in differentiated fibroblasts in long-term culture Stewart, Emma R. Turner, Robert M. L. Newling, Katherine Ridings-Figueroa, Rebeca Scott, Victoria Ashton, Peter D. Ainscough, Justin F. X. Coverley, Dawn Nat Commun Article 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. Nature Publishing Group UK 2019-01-28 /pmc/articles/PMC6484225/ /pubmed/30692537 http://dx.doi.org/10.1038/s41467-018-08072-2 Text en © Crown 2019 Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/.
spellingShingle Article
Stewart, Emma R.
Turner, Robert M. L.
Newling, Katherine
Ridings-Figueroa, Rebeca
Scott, Victoria
Ashton, Peter D.
Ainscough, Justin F. X.
Coverley, Dawn
Maintenance of epigenetic landscape requires CIZ1 and is corrupted in differentiated fibroblasts in long-term culture
title Maintenance of epigenetic landscape requires CIZ1 and is corrupted in differentiated fibroblasts in long-term culture
title_full Maintenance of epigenetic landscape requires CIZ1 and is corrupted in differentiated fibroblasts in long-term culture
title_fullStr Maintenance of epigenetic landscape requires CIZ1 and is corrupted in differentiated fibroblasts in long-term culture
title_full_unstemmed Maintenance of epigenetic landscape requires CIZ1 and is corrupted in differentiated fibroblasts in long-term culture
title_short Maintenance of epigenetic landscape requires CIZ1 and is corrupted in differentiated fibroblasts in long-term culture
title_sort maintenance of epigenetic landscape requires ciz1 and is corrupted in differentiated fibroblasts in long-term culture
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6484225/
https://www.ncbi.nlm.nih.gov/pubmed/30692537
http://dx.doi.org/10.1038/s41467-018-08072-2
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