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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...

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Autores principales: Sofi, Sajad, Williamson, Louisa, Turvey, Gabrielle L., Scoynes, Charlotte, Hirst, Claire, Godwin, Jonathan, Brockdorff, Neil, Ainscough, Justin, Coverley, Dawn
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Rockefeller University Press 2022
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.
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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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