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Adr1 and Cat8 mediate coactivator recruitment and chromatin remodeling at glucose-regulated genes.

Biddick RK, Law GL, Young ET - PLoS ONE (2008)

Bottom Line: We determined the individual contributions of Cat8 and Adr1 on the expression of a cohort of glucose-repressed genes and found three broad categories: genes that need both activators for full derepression, genes that rely mostly on Cat8 and genes that require only Adr1.These promoter-specific contributions are also apparent in the chromatin remodeling that accompanies derepression: ADH2 requires both Adr1 and Cat8, whereas, at FBP1, significant remodeling occurs with Cat8 alone.Thus, at many of the glucose-repressed genes, Cat8 and Adr1 appear to have interchangeable roles and promoter architecture may dictate the roles of these activators.

View Article: PubMed Central - PubMed

Affiliation: Department of Biochemistry, University of Washington, Seattle, Washington, United States of America.

ABSTRACT

Background: Adr1 and Cat8 co-regulate numerous glucose-repressed genes in S. cerevisiae, presenting a unique opportunity to explore their individual roles in coactivator recruitment, chromatin remodeling, and transcription.

Methodology/principal findings: We determined the individual contributions of Cat8 and Adr1 on the expression of a cohort of glucose-repressed genes and found three broad categories: genes that need both activators for full derepression, genes that rely mostly on Cat8 and genes that require only Adr1. Through combined expression and recruitment data, along with analysis of chromatin remodeling at two of these genes, ADH2 and FBP1, we clarified how these activators achieve this wide range of co-regulation. We find that Adr1 and Cat8 are not intrinsically different in their abilities to recruit coactivators but rather, promoter context appears to dictate which activator is responsible for recruitment to specific genes. These promoter-specific contributions are also apparent in the chromatin remodeling that accompanies derepression: ADH2 requires both Adr1 and Cat8, whereas, at FBP1, significant remodeling occurs with Cat8 alone. Although over-expression of Adr1 can compensate for loss of Cat8 at many genes in terms of both activation and chromatin remodeling, this over-expression cannot complement all of the cat8Delta phenotypes.

Conclusions/significance: Thus, at many of the glucose-repressed genes, Cat8 and Adr1 appear to have interchangeable roles and promoter architecture may dictate the roles of these activators.

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Related in: MedlinePlus

Adr1 and Cat8 play different roles at ADH2 and FBP1.Comparison between the ADH2 (A and C, orange) and FBP1 (B and D, blue) promoters in either adr1Δ (A and B) or a cat8Δ (C and D). Combined expression, recruitment and chromatin remodeling data at 4 hours of derepression are shown. Values in parenthesis indicate the percent binding of the wild-type derepressed value, after normalization (an asterisk represents previously published data [9]). Gene activation is reported as the percent of the wild-type derepressed level. Binding sites are shown at their approximate locations along the promoter (Cat8 in green, Adr1 in pink, and TATA box in blue). Nucleosome positions under derepressed conditions are depicted as shaded ovals on the promoter, and the degree of chromatin remodeling estimated as a percent of the remodeling observed in a wild-type strain. Locations of coactivators are not intended to reflect interactions.
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pone-0001436-g003: Adr1 and Cat8 play different roles at ADH2 and FBP1.Comparison between the ADH2 (A and C, orange) and FBP1 (B and D, blue) promoters in either adr1Δ (A and B) or a cat8Δ (C and D). Combined expression, recruitment and chromatin remodeling data at 4 hours of derepression are shown. Values in parenthesis indicate the percent binding of the wild-type derepressed value, after normalization (an asterisk represents previously published data [9]). Gene activation is reported as the percent of the wild-type derepressed level. Binding sites are shown at their approximate locations along the promoter (Cat8 in green, Adr1 in pink, and TATA box in blue). Nucleosome positions under derepressed conditions are depicted as shaded ovals on the promoter, and the degree of chromatin remodeling estimated as a percent of the remodeling observed in a wild-type strain. Locations of coactivators are not intended to reflect interactions.

Mentions: The possibility that these two activators made unique contributions via their ability to recruit different coactivators is ruled out through our extensive ChIP experiments, demonstrating that both Adr1 and Cat8 are capable of recruiting any of the coactivators we studied. Figure 3 summarizes the roles of Adr1 and Cat8 at two contrasting genes, ADH2 (A and C) and FBP1 (B and D). The fact that Mediator, for example, is recruited largely by Adr1 at ADH2, but by Cat8 at FBP1 argues that protein-protein interactions are not the governing principle, but rather that it is promoter context that dictates which transcription factor dominates these interactions (see below).


Adr1 and Cat8 mediate coactivator recruitment and chromatin remodeling at glucose-regulated genes.

Biddick RK, Law GL, Young ET - PLoS ONE (2008)

Adr1 and Cat8 play different roles at ADH2 and FBP1.Comparison between the ADH2 (A and C, orange) and FBP1 (B and D, blue) promoters in either adr1Δ (A and B) or a cat8Δ (C and D). Combined expression, recruitment and chromatin remodeling data at 4 hours of derepression are shown. Values in parenthesis indicate the percent binding of the wild-type derepressed value, after normalization (an asterisk represents previously published data [9]). Gene activation is reported as the percent of the wild-type derepressed level. Binding sites are shown at their approximate locations along the promoter (Cat8 in green, Adr1 in pink, and TATA box in blue). Nucleosome positions under derepressed conditions are depicted as shaded ovals on the promoter, and the degree of chromatin remodeling estimated as a percent of the remodeling observed in a wild-type strain. Locations of coactivators are not intended to reflect interactions.
© Copyright Policy
Related In: Results  -  Collection

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getmorefigures.php?uid=PMC2175534&req=5

pone-0001436-g003: Adr1 and Cat8 play different roles at ADH2 and FBP1.Comparison between the ADH2 (A and C, orange) and FBP1 (B and D, blue) promoters in either adr1Δ (A and B) or a cat8Δ (C and D). Combined expression, recruitment and chromatin remodeling data at 4 hours of derepression are shown. Values in parenthesis indicate the percent binding of the wild-type derepressed value, after normalization (an asterisk represents previously published data [9]). Gene activation is reported as the percent of the wild-type derepressed level. Binding sites are shown at their approximate locations along the promoter (Cat8 in green, Adr1 in pink, and TATA box in blue). Nucleosome positions under derepressed conditions are depicted as shaded ovals on the promoter, and the degree of chromatin remodeling estimated as a percent of the remodeling observed in a wild-type strain. Locations of coactivators are not intended to reflect interactions.
Mentions: The possibility that these two activators made unique contributions via their ability to recruit different coactivators is ruled out through our extensive ChIP experiments, demonstrating that both Adr1 and Cat8 are capable of recruiting any of the coactivators we studied. Figure 3 summarizes the roles of Adr1 and Cat8 at two contrasting genes, ADH2 (A and C) and FBP1 (B and D). The fact that Mediator, for example, is recruited largely by Adr1 at ADH2, but by Cat8 at FBP1 argues that protein-protein interactions are not the governing principle, but rather that it is promoter context that dictates which transcription factor dominates these interactions (see below).

Bottom Line: We determined the individual contributions of Cat8 and Adr1 on the expression of a cohort of glucose-repressed genes and found three broad categories: genes that need both activators for full derepression, genes that rely mostly on Cat8 and genes that require only Adr1.These promoter-specific contributions are also apparent in the chromatin remodeling that accompanies derepression: ADH2 requires both Adr1 and Cat8, whereas, at FBP1, significant remodeling occurs with Cat8 alone.Thus, at many of the glucose-repressed genes, Cat8 and Adr1 appear to have interchangeable roles and promoter architecture may dictate the roles of these activators.

View Article: PubMed Central - PubMed

Affiliation: Department of Biochemistry, University of Washington, Seattle, Washington, United States of America.

ABSTRACT

Background: Adr1 and Cat8 co-regulate numerous glucose-repressed genes in S. cerevisiae, presenting a unique opportunity to explore their individual roles in coactivator recruitment, chromatin remodeling, and transcription.

Methodology/principal findings: We determined the individual contributions of Cat8 and Adr1 on the expression of a cohort of glucose-repressed genes and found three broad categories: genes that need both activators for full derepression, genes that rely mostly on Cat8 and genes that require only Adr1. Through combined expression and recruitment data, along with analysis of chromatin remodeling at two of these genes, ADH2 and FBP1, we clarified how these activators achieve this wide range of co-regulation. We find that Adr1 and Cat8 are not intrinsically different in their abilities to recruit coactivators but rather, promoter context appears to dictate which activator is responsible for recruitment to specific genes. These promoter-specific contributions are also apparent in the chromatin remodeling that accompanies derepression: ADH2 requires both Adr1 and Cat8, whereas, at FBP1, significant remodeling occurs with Cat8 alone. Although over-expression of Adr1 can compensate for loss of Cat8 at many genes in terms of both activation and chromatin remodeling, this over-expression cannot complement all of the cat8Delta phenotypes.

Conclusions/significance: Thus, at many of the glucose-repressed genes, Cat8 and Adr1 appear to have interchangeable roles and promoter architecture may dictate the roles of these activators.

Show MeSH
Related in: MedlinePlus