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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...

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Autores principales: Singer, Ruth, Atar, Shimshi, Atias, Osnat, Oron, Efrat, Segal, Daniel, Hirsch, Joel A., Tuller, Tamir, Orian, Amir, Chamovitz, Daniel A.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Oxford University Press 2014
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.
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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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