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Nucleic Acids Res. 2014 Sep;42(15):9761-70. doi: 10.1093/nar/gku723. Epub 2014 Aug 8.

Drosophila COP9 signalosome subunit 7 interacts with multiple genomic loci to regulate development.

Author information

1
Department of Molecular Biology and Ecology of Plants.
2
Department of Biomedical Engineering.
3
Department of Molecular Microbiology and Biotechnology.
4
Department of Biochemistry and Molecular Biology, Tel Aviv University, Ramat Aviv, Tel Aviv 69978, Israel.
5
Cancer and Vascular Biology Research Center, Faculty of Medicine, Technion-Israel Institute of Technology, Haifa, Israel.
6
Department of Molecular Biology and Ecology of Plants dannyc@tauex.tau.ac.il.

Abstract

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.

PMID:
25106867
PMCID:
PMC4150811
DOI:
10.1093/nar/gku723
[Indexed for MEDLINE]
Free PMC Article

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