Limits...
Transcriptional responses to fatty acid are coordinated by combinatorial control.

Smith JJ, Ramsey SA, Marelli M, Marzolf B, Hwang D, Saleem RA, Rachubinski RA, Aitchison JD - Mol. Syst. Biol. (2007)

Bottom Line: By analyzing trends in the network structure, we found that two groups of multi-input motifs form in response to oleate, each controlling distinct functional classes of genes.The dynamic cooperation between Oaf1p and Pip2p appears to temporally synchronize the two different responses.Together, these data suggest a network mechanism involving dynamic combinatorial control for coordinating transcriptional responses.

View Article: PubMed Central - PubMed

Affiliation: Institute for Systems Biology, Seattle, WA 98103-8904, USA.

ABSTRACT
In transcriptional regulatory networks, the coincident binding of a combination of factors to regulate a gene implies the existence of complex mechanisms to control both the gene expression profile and specificity of the response. Unraveling this complexity is a major challenge to biologists. Here, a novel network topology-based clustering approach was applied to condition-specific genome-wide chromatin localization and expression data to characterize a dynamic transcriptional regulatory network responsive to the fatty acid oleate. A network of four (predicted) regulators of the response (Oaf1p, Pip2p, Adr1p and Oaf3p) was investigated. By analyzing trends in the network structure, we found that two groups of multi-input motifs form in response to oleate, each controlling distinct functional classes of genes. This functionality is contributed in part by Oaf1p, which is a component of both types of multi-input motifs and has two different regulatory activities depending on its binding context. The dynamic cooperation between Oaf1p and Pip2p appears to temporally synchronize the two different responses. Together, these data suggest a network mechanism involving dynamic combinatorial control for coordinating transcriptional responses.

Show MeSH
Network topology reflects target gene expression profile and function. (A) Oleate-responsive genes cluster into five groups based on their expression profiles (Koerkamp et al, 2002). The mean profiles of three gene clusters relevant to the regulatory network are shown and are annotated with biological processes associated with them. (B, C) Statistical analysis of the network distribution of the peroxisome-related (B) and the general stress response (C) expression profile clusters. Network topology clusters with an overrepresentation of peroxisome-related genes and general stress response genes have dark orange and dark blue bars, respectively. The height of each bar reflects the significance of the enrichment. In the presence of oleate, topology cluster AOY (genes targeted by Adr1p, Oaf1p and Oaf3p) is significantly enriched for the expression cluster representing general stress response genes (P-value∼5 × 10−7), whereas topology cluster OPY (genes targeted by Oaf1p, Pip2p and Oaf3p) is enriched for expression cluster representing peroxisome-related genes (P-value∼2 × 10−6). For both expression clusters, significance scores are lower and targeting is less cooperative in the glucose network. Statistical analyses of the distributions of OREs and Msn2p/Msn4p binding sites in the networks are also shown. These data are similar to those of the peroxisome-related and general stress response genes, respectively.
© Copyright Policy - open-access
Related In: Results  -  Collection

License
getmorefigures.php?uid=PMC1911199&req=5

f2: Network topology reflects target gene expression profile and function. (A) Oleate-responsive genes cluster into five groups based on their expression profiles (Koerkamp et al, 2002). The mean profiles of three gene clusters relevant to the regulatory network are shown and are annotated with biological processes associated with them. (B, C) Statistical analysis of the network distribution of the peroxisome-related (B) and the general stress response (C) expression profile clusters. Network topology clusters with an overrepresentation of peroxisome-related genes and general stress response genes have dark orange and dark blue bars, respectively. The height of each bar reflects the significance of the enrichment. In the presence of oleate, topology cluster AOY (genes targeted by Adr1p, Oaf1p and Oaf3p) is significantly enriched for the expression cluster representing general stress response genes (P-value∼5 × 10−7), whereas topology cluster OPY (genes targeted by Oaf1p, Pip2p and Oaf3p) is enriched for expression cluster representing peroxisome-related genes (P-value∼2 × 10−6). For both expression clusters, significance scores are lower and targeting is less cooperative in the glucose network. Statistical analyses of the distributions of OREs and Msn2p/Msn4p binding sites in the networks are also shown. These data are similar to those of the peroxisome-related and general stress response genes, respectively.

Mentions: The first gene properties measured were the results of a time-course transcriptome profiling study (Koerkamp et al, 2002), which was conducted under conditions similar to those of the ChIP experiments performed here (i.e. carbon source was switched from low glucose to oleate). For this analysis, several measurements were obtained within minutes after the switch to oleate, a time when transcription appears to be changing most rapidly; thus they classified responses that might otherwise be indistinguishable. This study identified five distinct expression profile clusters of oleate-responsive genes, and integration of gene ontology (GO) and DNA motif data revealed that the expression clusters represented different biological processes including oxidative stress response, general stress response and peroxisome biology (Figure 2A).


Transcriptional responses to fatty acid are coordinated by combinatorial control.

Smith JJ, Ramsey SA, Marelli M, Marzolf B, Hwang D, Saleem RA, Rachubinski RA, Aitchison JD - Mol. Syst. Biol. (2007)

Network topology reflects target gene expression profile and function. (A) Oleate-responsive genes cluster into five groups based on their expression profiles (Koerkamp et al, 2002). The mean profiles of three gene clusters relevant to the regulatory network are shown and are annotated with biological processes associated with them. (B, C) Statistical analysis of the network distribution of the peroxisome-related (B) and the general stress response (C) expression profile clusters. Network topology clusters with an overrepresentation of peroxisome-related genes and general stress response genes have dark orange and dark blue bars, respectively. The height of each bar reflects the significance of the enrichment. In the presence of oleate, topology cluster AOY (genes targeted by Adr1p, Oaf1p and Oaf3p) is significantly enriched for the expression cluster representing general stress response genes (P-value∼5 × 10−7), whereas topology cluster OPY (genes targeted by Oaf1p, Pip2p and Oaf3p) is enriched for expression cluster representing peroxisome-related genes (P-value∼2 × 10−6). For both expression clusters, significance scores are lower and targeting is less cooperative in the glucose network. Statistical analyses of the distributions of OREs and Msn2p/Msn4p binding sites in the networks are also shown. These data are similar to those of the peroxisome-related and general stress response genes, respectively.
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC1911199&req=5

f2: Network topology reflects target gene expression profile and function. (A) Oleate-responsive genes cluster into five groups based on their expression profiles (Koerkamp et al, 2002). The mean profiles of three gene clusters relevant to the regulatory network are shown and are annotated with biological processes associated with them. (B, C) Statistical analysis of the network distribution of the peroxisome-related (B) and the general stress response (C) expression profile clusters. Network topology clusters with an overrepresentation of peroxisome-related genes and general stress response genes have dark orange and dark blue bars, respectively. The height of each bar reflects the significance of the enrichment. In the presence of oleate, topology cluster AOY (genes targeted by Adr1p, Oaf1p and Oaf3p) is significantly enriched for the expression cluster representing general stress response genes (P-value∼5 × 10−7), whereas topology cluster OPY (genes targeted by Oaf1p, Pip2p and Oaf3p) is enriched for expression cluster representing peroxisome-related genes (P-value∼2 × 10−6). For both expression clusters, significance scores are lower and targeting is less cooperative in the glucose network. Statistical analyses of the distributions of OREs and Msn2p/Msn4p binding sites in the networks are also shown. These data are similar to those of the peroxisome-related and general stress response genes, respectively.
Mentions: The first gene properties measured were the results of a time-course transcriptome profiling study (Koerkamp et al, 2002), which was conducted under conditions similar to those of the ChIP experiments performed here (i.e. carbon source was switched from low glucose to oleate). For this analysis, several measurements were obtained within minutes after the switch to oleate, a time when transcription appears to be changing most rapidly; thus they classified responses that might otherwise be indistinguishable. This study identified five distinct expression profile clusters of oleate-responsive genes, and integration of gene ontology (GO) and DNA motif data revealed that the expression clusters represented different biological processes including oxidative stress response, general stress response and peroxisome biology (Figure 2A).

Bottom Line: By analyzing trends in the network structure, we found that two groups of multi-input motifs form in response to oleate, each controlling distinct functional classes of genes.The dynamic cooperation between Oaf1p and Pip2p appears to temporally synchronize the two different responses.Together, these data suggest a network mechanism involving dynamic combinatorial control for coordinating transcriptional responses.

View Article: PubMed Central - PubMed

Affiliation: Institute for Systems Biology, Seattle, WA 98103-8904, USA.

ABSTRACT
In transcriptional regulatory networks, the coincident binding of a combination of factors to regulate a gene implies the existence of complex mechanisms to control both the gene expression profile and specificity of the response. Unraveling this complexity is a major challenge to biologists. Here, a novel network topology-based clustering approach was applied to condition-specific genome-wide chromatin localization and expression data to characterize a dynamic transcriptional regulatory network responsive to the fatty acid oleate. A network of four (predicted) regulators of the response (Oaf1p, Pip2p, Adr1p and Oaf3p) was investigated. By analyzing trends in the network structure, we found that two groups of multi-input motifs form in response to oleate, each controlling distinct functional classes of genes. This functionality is contributed in part by Oaf1p, which is a component of both types of multi-input motifs and has two different regulatory activities depending on its binding context. The dynamic cooperation between Oaf1p and Pip2p appears to temporally synchronize the two different responses. Together, these data suggest a network mechanism involving dynamic combinatorial control for coordinating transcriptional responses.

Show MeSH