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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.

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Related in: MedlinePlus

Sequential changes in protein levels reflect coordination of responses by the network. FACS analysis of various GFP-tagged strains corresponding to genes under combinatorial control in the oleate network (topologies listed on the left). For each strain, fluorescence intensities of cells grown in glycerol (blue curves) were compared to those induced in oleate for 5 or 20 h (red curves). Protein levels corresponding to genes of the AOY topology are reduced in the presence of oleate, whereas those corresponding to genes with AOPY and OPY topologies increase after oleate induction. The negative effect of oleate on AOY gene expression is apparent after short and long induction periods, whereas the upregulation of gene targeted by Oaf1p and Pip2p is observed only after long induction periods.
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f6: Sequential changes in protein levels reflect coordination of responses by the network. FACS analysis of various GFP-tagged strains corresponding to genes under combinatorial control in the oleate network (topologies listed on the left). For each strain, fluorescence intensities of cells grown in glycerol (blue curves) were compared to those induced in oleate for 5 or 20 h (red curves). Protein levels corresponding to genes of the AOY topology are reduced in the presence of oleate, whereas those corresponding to genes with AOPY and OPY topologies increase after oleate induction. The negative effect of oleate on AOY gene expression is apparent after short and long induction periods, whereas the upregulation of gene targeted by Oaf1p and Pip2p is observed only after long induction periods.

Mentions: To explore the potential for temporal coordination of the network, representative GFP-tagged strains were analyzed by FACS after growth in the absence of oleate (YPBG) and after 5 and 20 h inductions in the presence of oleate (YPBO) (Figure 6). Consistent with the gene expression data (Figure 3A), levels of proteins corresponding to the AOY cluster decreased in the presence of oleate, whereas those corresponding to the OPY and AOPY clusters increased in response to oleate. Interestingly, although the decreases in expression were clear after a 5-h induction, increases in expression were prominent after 20 h in oleate. These data appear to reflect the fact that the transcriptional response of general stress response genes precedes that of the peroxisome-related genes as identified previously by microarray analysis (Koerkamp et al, 2002) (Figure 2A). This suggests temporal coordination of the two biological processes and provides insight into the function of the network as described in Discussion.


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)

Sequential changes in protein levels reflect coordination of responses by the network. FACS analysis of various GFP-tagged strains corresponding to genes under combinatorial control in the oleate network (topologies listed on the left). For each strain, fluorescence intensities of cells grown in glycerol (blue curves) were compared to those induced in oleate for 5 or 20 h (red curves). Protein levels corresponding to genes of the AOY topology are reduced in the presence of oleate, whereas those corresponding to genes with AOPY and OPY topologies increase after oleate induction. The negative effect of oleate on AOY gene expression is apparent after short and long induction periods, whereas the upregulation of gene targeted by Oaf1p and Pip2p is observed only after long induction periods.
© Copyright Policy - open-access
Related In: Results  -  Collection

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

f6: Sequential changes in protein levels reflect coordination of responses by the network. FACS analysis of various GFP-tagged strains corresponding to genes under combinatorial control in the oleate network (topologies listed on the left). For each strain, fluorescence intensities of cells grown in glycerol (blue curves) were compared to those induced in oleate for 5 or 20 h (red curves). Protein levels corresponding to genes of the AOY topology are reduced in the presence of oleate, whereas those corresponding to genes with AOPY and OPY topologies increase after oleate induction. The negative effect of oleate on AOY gene expression is apparent after short and long induction periods, whereas the upregulation of gene targeted by Oaf1p and Pip2p is observed only after long induction periods.
Mentions: To explore the potential for temporal coordination of the network, representative GFP-tagged strains were analyzed by FACS after growth in the absence of oleate (YPBG) and after 5 and 20 h inductions in the presence of oleate (YPBO) (Figure 6). Consistent with the gene expression data (Figure 3A), levels of proteins corresponding to the AOY cluster decreased in the presence of oleate, whereas those corresponding to the OPY and AOPY clusters increased in response to oleate. Interestingly, although the decreases in expression were clear after a 5-h induction, increases in expression were prominent after 20 h in oleate. These data appear to reflect the fact that the transcriptional response of general stress response genes precedes that of the peroxisome-related genes as identified previously by microarray analysis (Koerkamp et al, 2002) (Figure 2A). This suggests temporal coordination of the two biological processes and provides insight into the function of the network as described in Discussion.

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
Related in: MedlinePlus