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

Singer R, Atar S, Atias O, Oron E, Segal D, Hirsch JA, Tuller T, Orian A, Chamovitz DA - Nucleic Acids Res. (2014)

Bottom Line: 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.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.

View Article: PubMed Central - PubMed

Affiliation: Department of Molecular Biology and Ecology of Plants.

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(A and B) Silencing Csn7 affects patterning of the wing imaginal disc. Silencing Csn7 (B) results in changes of the wing disc compared to control (A). The folds in the wing disc are clearly seen in the confocal image of the control disc stained with α-CSN7 or Hoechst, but not when CSN7 is silenced. CSN7 is not detected in (A). (C and D) Cell-cycle profiles of cells dissociated from wing discs expressing the UAS-RNAi-CSN7 construct under the control of the Act- (C) or En- (D) Gal4 (red) relative to profiles of dissociated cells from wing discs expressing the Act or En-Gal4 drivers alone (green). (E) Cell-cycle profile of SR+ cells silenced for CSN7 using CSN7-RNAi (red) relative to control cells (green). (F) Cell-cycle profiles of cells from dissociated wing discs expressing the Act>RNAi-Csn2 and Act>RNAi-Csn8.
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Figure 3: (A and B) Silencing Csn7 affects patterning of the wing imaginal disc. Silencing Csn7 (B) results in changes of the wing disc compared to control (A). The folds in the wing disc are clearly seen in the confocal image of the control disc stained with α-CSN7 or Hoechst, but not when CSN7 is silenced. CSN7 is not detected in (A). (C and D) Cell-cycle profiles of cells dissociated from wing discs expressing the UAS-RNAi-CSN7 construct under the control of the Act- (C) or En- (D) Gal4 (red) relative to profiles of dissociated cells from wing discs expressing the Act or En-Gal4 drivers alone (green). (E) Cell-cycle profile of SR+ cells silenced for CSN7 using CSN7-RNAi (red) relative to control cells (green). (F) Cell-cycle profiles of cells from dissociated wing discs expressing the Act>RNAi-Csn2 and Act>RNAi-Csn8.

Mentions: Next, we examined the role of CSN7 in imaginal disc formation and cell-cycle progression, two of the GO groupings identified as enriched in CSN7-DamID targets. Imaginal wing discs in third instar csn7p larvae are severely reduced in size, which correlates with the enrichment of genes associated with imaginal discs identified by DamID. As the size of the imaginal wing discs from the csn7 p mutant discs precluded further analyses, we specifically targeted CSN7 using UAS-Csn7-RNAi transgene under either Act-Gal4 or En-Gal4. While these wing discs were of normal size, they were developmentally defective as the folds in the wing pouch and hinge were not readily evident (Figure 3A and B).


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

Singer R, Atar S, Atias O, Oron E, Segal D, Hirsch JA, Tuller T, Orian A, Chamovitz DA - Nucleic Acids Res. (2014)

(A and B) Silencing Csn7 affects patterning of the wing imaginal disc. Silencing Csn7 (B) results in changes of the wing disc compared to control (A). The folds in the wing disc are clearly seen in the confocal image of the control disc stained with α-CSN7 or Hoechst, but not when CSN7 is silenced. CSN7 is not detected in (A). (C and D) Cell-cycle profiles of cells dissociated from wing discs expressing the UAS-RNAi-CSN7 construct under the control of the Act- (C) or En- (D) Gal4 (red) relative to profiles of dissociated cells from wing discs expressing the Act or En-Gal4 drivers alone (green). (E) Cell-cycle profile of SR+ cells silenced for CSN7 using CSN7-RNAi (red) relative to control cells (green). (F) Cell-cycle profiles of cells from dissociated wing discs expressing the Act>RNAi-Csn2 and Act>RNAi-Csn8.
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Figure 3: (A and B) Silencing Csn7 affects patterning of the wing imaginal disc. Silencing Csn7 (B) results in changes of the wing disc compared to control (A). The folds in the wing disc are clearly seen in the confocal image of the control disc stained with α-CSN7 or Hoechst, but not when CSN7 is silenced. CSN7 is not detected in (A). (C and D) Cell-cycle profiles of cells dissociated from wing discs expressing the UAS-RNAi-CSN7 construct under the control of the Act- (C) or En- (D) Gal4 (red) relative to profiles of dissociated cells from wing discs expressing the Act or En-Gal4 drivers alone (green). (E) Cell-cycle profile of SR+ cells silenced for CSN7 using CSN7-RNAi (red) relative to control cells (green). (F) Cell-cycle profiles of cells from dissociated wing discs expressing the Act>RNAi-Csn2 and Act>RNAi-Csn8.
Mentions: Next, we examined the role of CSN7 in imaginal disc formation and cell-cycle progression, two of the GO groupings identified as enriched in CSN7-DamID targets. Imaginal wing discs in third instar csn7p larvae are severely reduced in size, which correlates with the enrichment of genes associated with imaginal discs identified by DamID. As the size of the imaginal wing discs from the csn7 p mutant discs precluded further analyses, we specifically targeted CSN7 using UAS-Csn7-RNAi transgene under either Act-Gal4 or En-Gal4. While these wing discs were of normal size, they were developmentally defective as the folds in the wing pouch and hinge were not readily evident (Figure 3A and B).

Bottom Line: 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.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.

View Article: PubMed Central - PubMed

Affiliation: Department of Molecular Biology and Ecology of Plants.

Show MeSH