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Drosophila COP9 signalosome subunit 7 interacts with multiple genomic loci to regulate development
The COP9 signalosome protein complex has a central role in the regulation of development of multicellular organisms. While the function of this complex in ubiquitin-mediated protein degradation is well established, results over the past few years have hinted that the COP9 signalosome may function mo...
Autores principales: | , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Oxford University Press
2014
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4150811/ https://www.ncbi.nlm.nih.gov/pubmed/25106867 http://dx.doi.org/10.1093/nar/gku723 |
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author | Singer, Ruth Atar, Shimshi Atias, Osnat Oron, Efrat Segal, Daniel Hirsch, Joel A. Tuller, Tamir Orian, Amir Chamovitz, Daniel A. |
author_facet | Singer, Ruth Atar, Shimshi Atias, Osnat Oron, Efrat Segal, Daniel Hirsch, Joel A. Tuller, Tamir Orian, Amir Chamovitz, Daniel A. |
author_sort | Singer, Ruth |
collection | PubMed |
description | The COP9 signalosome protein complex has a central role in the regulation of development of multicellular organisms. While the function of this complex in ubiquitin-mediated protein degradation is well established, results over the past few years have hinted that the COP9 signalosome may function more broadly in the regulation of gene expression. Here, using DamID technology, we show that COP9 signalosome subunit 7 functionally associates with a large number of genomic loci in the Drosophila genome, and show that the expression of many genes within these loci is COP9 signalosome-dependent. This association is likely direct as we show CSN7 binds DNA in vitro. The genes targeted by CSN7 are preferentially enriched for transcriptionally active regions of the genome, and are involved in the regulation of distinct gene ontology groupings including imaginal disc development and cell-cycle control. In accord, loss of CSN7 function leads to cell-cycle delay and altered wing development. These results indicate that CSN7, and by extension the entire COP9 signalosome, functions directly in transcriptional control. While the COP9 signalosome protein complex has long been known to regulate protein degradation, here we expand the role of this complex by showing that subunit 7 binds DNA in vitro and functions directly in vivo in transcriptional control of developmentally important pathways that are relevant for human health. |
format | Online Article Text |
id | pubmed-4150811 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2014 |
publisher | Oxford University Press |
record_format | MEDLINE/PubMed |
spelling | pubmed-41508112014-12-01 Drosophila COP9 signalosome subunit 7 interacts with multiple genomic loci to regulate development Singer, Ruth Atar, Shimshi Atias, Osnat Oron, Efrat Segal, Daniel Hirsch, Joel A. Tuller, Tamir Orian, Amir Chamovitz, Daniel A. Nucleic Acids Res Gene regulation, Chromatin and Epigenetics The COP9 signalosome protein complex has a central role in the regulation of development of multicellular organisms. While the function of this complex in ubiquitin-mediated protein degradation is well established, results over the past few years have hinted that the COP9 signalosome may function more broadly in the regulation of gene expression. Here, using DamID technology, we show that COP9 signalosome subunit 7 functionally associates with a large number of genomic loci in the Drosophila genome, and show that the expression of many genes within these loci is COP9 signalosome-dependent. This association is likely direct as we show CSN7 binds DNA in vitro. The genes targeted by CSN7 are preferentially enriched for transcriptionally active regions of the genome, and are involved in the regulation of distinct gene ontology groupings including imaginal disc development and cell-cycle control. In accord, loss of CSN7 function leads to cell-cycle delay and altered wing development. These results indicate that CSN7, and by extension the entire COP9 signalosome, functions directly in transcriptional control. While the COP9 signalosome protein complex has long been known to regulate protein degradation, here we expand the role of this complex by showing that subunit 7 binds DNA in vitro and functions directly in vivo in transcriptional control of developmentally important pathways that are relevant for human health. Oxford University Press 2014-09-02 2014-08-08 /pmc/articles/PMC4150811/ /pubmed/25106867 http://dx.doi.org/10.1093/nar/gku723 Text en © The Author(s) 2014. Published by Oxford University Press on behalf of Nucleic Acids Research. http://creativecommons.org/licenses/by-nc/4.0/ This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by-nc/4.0/), which permits non-commercial re-use, distribution, and reproduction in any medium, provided the original work is properly cited. For commercial re-use, please contact journals.permissions@oup.com |
spellingShingle | Gene regulation, Chromatin and Epigenetics Singer, Ruth Atar, Shimshi Atias, Osnat Oron, Efrat Segal, Daniel Hirsch, Joel A. Tuller, Tamir Orian, Amir Chamovitz, Daniel A. Drosophila COP9 signalosome subunit 7 interacts with multiple genomic loci to regulate development |
title |
Drosophila COP9 signalosome subunit 7 interacts with multiple genomic loci to regulate development |
title_full |
Drosophila COP9 signalosome subunit 7 interacts with multiple genomic loci to regulate development |
title_fullStr |
Drosophila COP9 signalosome subunit 7 interacts with multiple genomic loci to regulate development |
title_full_unstemmed |
Drosophila COP9 signalosome subunit 7 interacts with multiple genomic loci to regulate development |
title_short |
Drosophila COP9 signalosome subunit 7 interacts with multiple genomic loci to regulate development |
title_sort | drosophila cop9 signalosome subunit 7 interacts with multiple genomic loci to regulate development |
topic | Gene regulation, Chromatin and Epigenetics |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4150811/ https://www.ncbi.nlm.nih.gov/pubmed/25106867 http://dx.doi.org/10.1093/nar/gku723 |
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