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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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Analyses of the genes bound by CSN7 . (A) A global view on the DamID experiment. Black dots mark the positions of genes along the D. melanogaster genome; blue dots denote the positions of the most significant (top 10%) DamID signals; and red dots denote regions enriched in DamID signals, considering sliding windows of 1000 bp in length, and the top 49% of the scores. Dots are spaced minimally by 1000 bp. (B) CSN-dependent genes are preferentially enriched in the CSN7-DamID genes. Genes over- and underexpressed in csn mutants are significantly enriched in the CSN7-DamID results. Ten genes were both up- and downregulated, dependent on the mutant and stage; thus, the total number of genes in the graph (1770) is slightly larger than the actual total number of genes (1760). The P-values are based on hypergeometric distribution (which is based on the total number of genes, the number of gene in each set and the number of overlapping genes between the two sets). (C) Analyses of CSN7 enrichment in five chromatin types defined by Filion et al. (29) revealed a high overlap with ‘red’ and ‘yellow’ chromatin, while ‘black’ and ‘green’ chromatin were under-represented in the CSN7-DamID targets. ‘Blue’ chromatin was not affected by the CSN7-DamID. (D) Genes bound by CSN7 are significantly enriched in Rbf1 targets (P-value for overlap with CSN7-DamID: Embryo = 7.3255e−11, Larvae = 4.2188e−15).
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Figure 2: Analyses of the genes bound by CSN7 . (A) A global view on the DamID experiment. Black dots mark the positions of genes along the D. melanogaster genome; blue dots denote the positions of the most significant (top 10%) DamID signals; and red dots denote regions enriched in DamID signals, considering sliding windows of 1000 bp in length, and the top 49% of the scores. Dots are spaced minimally by 1000 bp. (B) CSN-dependent genes are preferentially enriched in the CSN7-DamID genes. Genes over- and underexpressed in csn mutants are significantly enriched in the CSN7-DamID results. Ten genes were both up- and downregulated, dependent on the mutant and stage; thus, the total number of genes in the graph (1770) is slightly larger than the actual total number of genes (1760). The P-values are based on hypergeometric distribution (which is based on the total number of genes, the number of gene in each set and the number of overlapping genes between the two sets). (C) Analyses of CSN7 enrichment in five chromatin types defined by Filion et al. (29) revealed a high overlap with ‘red’ and ‘yellow’ chromatin, while ‘black’ and ‘green’ chromatin were under-represented in the CSN7-DamID targets. ‘Blue’ chromatin was not affected by the CSN7-DamID. (D) Genes bound by CSN7 are significantly enriched in Rbf1 targets (P-value for overlap with CSN7-DamID: Embryo = 7.3255e−11, Larvae = 4.2188e−15).

Mentions: For Figure 2A, genes were divided into groups according to their fold change in the csn4 mutant at time 60 h AED (4). For each group the mean signal based on the CSN7 DamID experiment over the genomic region defined above was computed.


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)

Analyses of the genes bound by CSN7 . (A) A global view on the DamID experiment. Black dots mark the positions of genes along the D. melanogaster genome; blue dots denote the positions of the most significant (top 10%) DamID signals; and red dots denote regions enriched in DamID signals, considering sliding windows of 1000 bp in length, and the top 49% of the scores. Dots are spaced minimally by 1000 bp. (B) CSN-dependent genes are preferentially enriched in the CSN7-DamID genes. Genes over- and underexpressed in csn mutants are significantly enriched in the CSN7-DamID results. Ten genes were both up- and downregulated, dependent on the mutant and stage; thus, the total number of genes in the graph (1770) is slightly larger than the actual total number of genes (1760). The P-values are based on hypergeometric distribution (which is based on the total number of genes, the number of gene in each set and the number of overlapping genes between the two sets). (C) Analyses of CSN7 enrichment in five chromatin types defined by Filion et al. (29) revealed a high overlap with ‘red’ and ‘yellow’ chromatin, while ‘black’ and ‘green’ chromatin were under-represented in the CSN7-DamID targets. ‘Blue’ chromatin was not affected by the CSN7-DamID. (D) Genes bound by CSN7 are significantly enriched in Rbf1 targets (P-value for overlap with CSN7-DamID: Embryo = 7.3255e−11, Larvae = 4.2188e−15).
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Related In: Results  -  Collection

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Figure 2: Analyses of the genes bound by CSN7 . (A) A global view on the DamID experiment. Black dots mark the positions of genes along the D. melanogaster genome; blue dots denote the positions of the most significant (top 10%) DamID signals; and red dots denote regions enriched in DamID signals, considering sliding windows of 1000 bp in length, and the top 49% of the scores. Dots are spaced minimally by 1000 bp. (B) CSN-dependent genes are preferentially enriched in the CSN7-DamID genes. Genes over- and underexpressed in csn mutants are significantly enriched in the CSN7-DamID results. Ten genes were both up- and downregulated, dependent on the mutant and stage; thus, the total number of genes in the graph (1770) is slightly larger than the actual total number of genes (1760). The P-values are based on hypergeometric distribution (which is based on the total number of genes, the number of gene in each set and the number of overlapping genes between the two sets). (C) Analyses of CSN7 enrichment in five chromatin types defined by Filion et al. (29) revealed a high overlap with ‘red’ and ‘yellow’ chromatin, while ‘black’ and ‘green’ chromatin were under-represented in the CSN7-DamID targets. ‘Blue’ chromatin was not affected by the CSN7-DamID. (D) Genes bound by CSN7 are significantly enriched in Rbf1 targets (P-value for overlap with CSN7-DamID: Embryo = 7.3255e−11, Larvae = 4.2188e−15).
Mentions: For Figure 2A, genes were divided into groups according to their fold change in the csn4 mutant at time 60 h AED (4). For each group the mean signal based on the CSN7 DamID experiment over the genomic region defined above was computed.

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