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Prion-like domains drive CIZ1 assembly formation at the inactive X chromosome
CIZ1 forms large assemblies at the inactive X chromosome (Xi) in female fibroblasts in an Xist lncRNA-dependent manner and is required for accurate maintenance of polycomb targets genome-wide. Here we address requirements for assembly formation and show that CIZ1 undergoes two direct interactions wi...
Autores principales: | , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Rockefeller University Press
2022
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8927971/ https://www.ncbi.nlm.nih.gov/pubmed/35289833 http://dx.doi.org/10.1083/jcb.202103185 |
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author | Sofi, Sajad Williamson, Louisa Turvey, Gabrielle L. Scoynes, Charlotte Hirst, Claire Godwin, Jonathan Brockdorff, Neil Ainscough, Justin Coverley, Dawn |
author_facet | Sofi, Sajad Williamson, Louisa Turvey, Gabrielle L. Scoynes, Charlotte Hirst, Claire Godwin, Jonathan Brockdorff, Neil Ainscough, Justin Coverley, Dawn |
author_sort | Sofi, Sajad |
collection | PubMed |
description | CIZ1 forms large assemblies at the inactive X chromosome (Xi) in female fibroblasts in an Xist lncRNA-dependent manner and is required for accurate maintenance of polycomb targets genome-wide. Here we address requirements for assembly formation and show that CIZ1 undergoes two direct interactions with Xist, via independent N- and C-terminal domains. Interaction with Xist, assembly at Xi, and complexity of self-assemblies formed in vitro are modulated by two alternatively spliced glutamine-rich prion-like domains (PLD1 and 2). PLD2 is dispensable for accumulation at existing CIZ1–Xi assemblies in wild-type cells but is required in CIZ1-null cells where targeting, assembly, and enrichment for H3K27me3 and H2AK119ub occur de novo. In contrast, PLD1 is required for both de novo assembly and accumulation at preexisting assemblies and, in vitro, drives formation of a stable fibrillar network. Together they impart affinity for RNA and a complex relationship with repeat E of Xist. These data show that alternative splicing of two PLDs modulates CIZ1’s ability to build large RNA–protein assemblies. |
format | Online Article Text |
id | pubmed-8927971 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2022 |
publisher | Rockefeller University Press |
record_format | MEDLINE/PubMed |
spelling | pubmed-89279712022-03-18 Prion-like domains drive CIZ1 assembly formation at the inactive X chromosome Sofi, Sajad Williamson, Louisa Turvey, Gabrielle L. Scoynes, Charlotte Hirst, Claire Godwin, Jonathan Brockdorff, Neil Ainscough, Justin Coverley, Dawn J Cell Biol Article CIZ1 forms large assemblies at the inactive X chromosome (Xi) in female fibroblasts in an Xist lncRNA-dependent manner and is required for accurate maintenance of polycomb targets genome-wide. Here we address requirements for assembly formation and show that CIZ1 undergoes two direct interactions with Xist, via independent N- and C-terminal domains. Interaction with Xist, assembly at Xi, and complexity of self-assemblies formed in vitro are modulated by two alternatively spliced glutamine-rich prion-like domains (PLD1 and 2). PLD2 is dispensable for accumulation at existing CIZ1–Xi assemblies in wild-type cells but is required in CIZ1-null cells where targeting, assembly, and enrichment for H3K27me3 and H2AK119ub occur de novo. In contrast, PLD1 is required for both de novo assembly and accumulation at preexisting assemblies and, in vitro, drives formation of a stable fibrillar network. Together they impart affinity for RNA and a complex relationship with repeat E of Xist. These data show that alternative splicing of two PLDs modulates CIZ1’s ability to build large RNA–protein assemblies. Rockefeller University Press 2022-03-15 /pmc/articles/PMC8927971/ /pubmed/35289833 http://dx.doi.org/10.1083/jcb.202103185 Text en © 2022 Sofi et al. https://creativecommons.org/licenses/by/4.0/This article is available under a Creative Commons License (Attribution 4.0 International, as described at https://creativecommons.org/licenses/by/4.0/). |
spellingShingle | Article Sofi, Sajad Williamson, Louisa Turvey, Gabrielle L. Scoynes, Charlotte Hirst, Claire Godwin, Jonathan Brockdorff, Neil Ainscough, Justin Coverley, Dawn Prion-like domains drive CIZ1 assembly formation at the inactive X chromosome |
title | Prion-like domains drive CIZ1 assembly formation at the inactive X chromosome |
title_full | Prion-like domains drive CIZ1 assembly formation at the inactive X chromosome |
title_fullStr | Prion-like domains drive CIZ1 assembly formation at the inactive X chromosome |
title_full_unstemmed | Prion-like domains drive CIZ1 assembly formation at the inactive X chromosome |
title_short | Prion-like domains drive CIZ1 assembly formation at the inactive X chromosome |
title_sort | prion-like domains drive ciz1 assembly formation at the inactive x chromosome |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8927971/ https://www.ncbi.nlm.nih.gov/pubmed/35289833 http://dx.doi.org/10.1083/jcb.202103185 |
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