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The cockayne syndrome B protein is essential for neuronal differentiation and neuritogenesis
Cockayne syndrome (CS) is a progressive developmental and neurodegenerative disorder resulting in premature death at childhood and cells derived from CS patients display DNA repair and transcriptional defects. CS is caused by mutations in csa and csb genes, and patients with csb mutation are more pr...
Autores principales: | , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Nature Publishing Group
2014
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4047889/ https://www.ncbi.nlm.nih.gov/pubmed/24874740 http://dx.doi.org/10.1038/cddis.2014.228 |
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author | Ciaffardini, F Nicolai, S Caputo, M Canu, G Paccosi, E Costantino, M Frontini, M Balajee, A S Proietti-De-Santis, L |
author_facet | Ciaffardini, F Nicolai, S Caputo, M Canu, G Paccosi, E Costantino, M Frontini, M Balajee, A S Proietti-De-Santis, L |
author_sort | Ciaffardini, F |
collection | PubMed |
description | Cockayne syndrome (CS) is a progressive developmental and neurodegenerative disorder resulting in premature death at childhood and cells derived from CS patients display DNA repair and transcriptional defects. CS is caused by mutations in csa and csb genes, and patients with csb mutation are more prevalent. A hallmark feature of CSB patients is neurodegeneration but the precise molecular cause for this defect remains enigmatic. Further, it is not clear whether the neurodegenerative condition is due to loss of CSB-mediated functions in adult neurogenesis. In this study, we examined the role of CSB in neurogenesis by using the human neural progenitor cells that have self-renewal and differentiation capabilities. In this model system, stable CSB knockdown dramatically reduced the differentiation potential of human neural progenitor cells revealing a key role for CSB in neurogenesis. Neurite outgrowth, a characteristic feature of differentiated neurons, was also greatly abolished in CSB-suppressed cells. In corroboration with this, expression of MAP2 (microtubule-associated protein 2), a crucial player in neuritogenesis, was also impaired in CSB-suppressed cells. Consistent with reduced MAP2 expression in CSB-depleted neural cells, tandem affinity purification and chromatin immunoprecipitation studies revealed a potential role for CSB in the assembly of transcription complex on MAP2 promoter. Altogether, our data led us to conclude that CSB has a crucial role in coordinated regulation of transcription and chromatin remodeling activities that are required during neurogenesis. |
format | Online Article Text |
id | pubmed-4047889 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2014 |
publisher | Nature Publishing Group |
record_format | MEDLINE/PubMed |
spelling | pubmed-40478892014-06-12 The cockayne syndrome B protein is essential for neuronal differentiation and neuritogenesis Ciaffardini, F Nicolai, S Caputo, M Canu, G Paccosi, E Costantino, M Frontini, M Balajee, A S Proietti-De-Santis, L Cell Death Dis Original Article Cockayne syndrome (CS) is a progressive developmental and neurodegenerative disorder resulting in premature death at childhood and cells derived from CS patients display DNA repair and transcriptional defects. CS is caused by mutations in csa and csb genes, and patients with csb mutation are more prevalent. A hallmark feature of CSB patients is neurodegeneration but the precise molecular cause for this defect remains enigmatic. Further, it is not clear whether the neurodegenerative condition is due to loss of CSB-mediated functions in adult neurogenesis. In this study, we examined the role of CSB in neurogenesis by using the human neural progenitor cells that have self-renewal and differentiation capabilities. In this model system, stable CSB knockdown dramatically reduced the differentiation potential of human neural progenitor cells revealing a key role for CSB in neurogenesis. Neurite outgrowth, a characteristic feature of differentiated neurons, was also greatly abolished in CSB-suppressed cells. In corroboration with this, expression of MAP2 (microtubule-associated protein 2), a crucial player in neuritogenesis, was also impaired in CSB-suppressed cells. Consistent with reduced MAP2 expression in CSB-depleted neural cells, tandem affinity purification and chromatin immunoprecipitation studies revealed a potential role for CSB in the assembly of transcription complex on MAP2 promoter. Altogether, our data led us to conclude that CSB has a crucial role in coordinated regulation of transcription and chromatin remodeling activities that are required during neurogenesis. Nature Publishing Group 2014-05 2014-05-29 /pmc/articles/PMC4047889/ /pubmed/24874740 http://dx.doi.org/10.1038/cddis.2014.228 Text en Copyright © 2014 Macmillan Publishers Limited http://creativecommons.org/licenses/by-nc-nd/3.0/ Cell Death and Disease is an open-access journal published by Nature Publishing Group. This work is licensed under a Creative Commons Attribution-NonCommercial-NoDerivs 3.0 Unported License. The images or other third party material in this article are included in the article's Creative Commons license, unless indicated otherwise in the credit line; if the material is not included under the Creative Commons license, users will need to obtain permission from the license holder to reproduce the material. To view a copy of this license, visit http://creativecommons.org/licenses/by-nc-nd/3.0/ |
spellingShingle | Original Article Ciaffardini, F Nicolai, S Caputo, M Canu, G Paccosi, E Costantino, M Frontini, M Balajee, A S Proietti-De-Santis, L The cockayne syndrome B protein is essential for neuronal differentiation and neuritogenesis |
title | The cockayne syndrome B protein is essential for neuronal differentiation and neuritogenesis |
title_full | The cockayne syndrome B protein is essential for neuronal differentiation and neuritogenesis |
title_fullStr | The cockayne syndrome B protein is essential for neuronal differentiation and neuritogenesis |
title_full_unstemmed | The cockayne syndrome B protein is essential for neuronal differentiation and neuritogenesis |
title_short | The cockayne syndrome B protein is essential for neuronal differentiation and neuritogenesis |
title_sort | cockayne syndrome b protein is essential for neuronal differentiation and neuritogenesis |
topic | Original Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4047889/ https://www.ncbi.nlm.nih.gov/pubmed/24874740 http://dx.doi.org/10.1038/cddis.2014.228 |
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