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The yin and yang of yeast transcription: elements of a global feedback system between metabolism and chromatin.

Machné R, Murray DB - PLoS ONE (2012)

Bottom Line: We show that the ATP:ADP ratio oscillates, compatible with alternating metabolic activity of the two superclusters and differential feedback on their transcription via activating (RSC) and repressive (Isw2) types of promoter structure remodeling.We propose a novel feedback mechanism, where the energetic state of the cell, reflected in the ATP:ADP ratio, gates the transcription of large, but functionally coherent groups of genes via differential effects of ATP-dependent nucleosome remodeling machineries.Besides providing a mechanistic hypothesis for the delayed negative feedback that results in the oscillatory phenotype, this mechanism may underpin the continuous adaptation of growth to environmental conditions.

View Article: PubMed Central - PubMed

Affiliation: Institute for Theoretical Chemistry, University of Vienna, Vienna, Austria. raim@tbi.univie.ac.at

ABSTRACT
When grown in continuous culture, budding yeast cells tend to synchronize their respiratory activity to form a stable oscillation that percolates throughout cellular physiology and involves the majority of the protein-coding transcriptome. Oscillations in batch culture and at single cell level support the idea that these dynamics constitute a general growth principle. The precise molecular mechanisms and biological functions of the oscillation remain elusive. Fourier analysis of transcriptome time series datasets from two different oscillation periods (0.7 h and 5 h) reveals seven distinct co-expression clusters common to both systems (34% of all yeast ORF), which consolidate into two superclusters when correlated with a compilation of 1,327 unrelated transcriptome datasets. These superclusters encode for cell growth and anabolism during the phase of high, and mitochondrial growth, catabolism and stress response during the phase of low oxygen uptake. The promoters of each cluster are characterized by different nucleotide contents, promoter nucleosome configurations, and dependence on ATP-dependent nucleosome remodeling complexes. We show that the ATP:ADP ratio oscillates, compatible with alternating metabolic activity of the two superclusters and differential feedback on their transcription via activating (RSC) and repressive (Isw2) types of promoter structure remodeling. We propose a novel feedback mechanism, where the energetic state of the cell, reflected in the ATP:ADP ratio, gates the transcription of large, but functionally coherent groups of genes via differential effects of ATP-dependent nucleosome remodeling machineries. Besides providing a mechanistic hypothesis for the delayed negative feedback that results in the oscillatory phenotype, this mechanism may underpin the continuous adaptation of growth to environmental conditions.

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Summary of results & proposed feedback model.7A: temporal flow of expression and functional relationships of cluster transcripts in the 0.7 h system (left to right) and the 5 h system (top to bottom). 7B: summary of observed properties (significant enrichment or biases) of the main gene clusters. 7C: Potential regulatory interactions of broad cellular functionality via the energetic status of the cell, reflected, e.g., in ATP:ADP ratios. In the oxidative phase catabolic activity leads to a high ATP synthesis rate. At high ATP:ADP ratios promoters of anabolic genes are active, potentially mediated by ATP-dependent nucleosome remodeling, which at the same time keeps promoters of catabolic genes in a repressed state. When respiratory activity suddenly slows down in the reductive phase the activity of the anabolic genes, i.e., amino acid and protein synthesis, leads to a decrease of the ATP:ADP ratio and the promoters of catabolic genes become active. Diverse cellular stresses may result in a sudden drop in the cellular ATP:ADP ratio due to the energetic costs of immediate biochemical stress response.
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pone-0037906-g007: Summary of results & proposed feedback model.7A: temporal flow of expression and functional relationships of cluster transcripts in the 0.7 h system (left to right) and the 5 h system (top to bottom). 7B: summary of observed properties (significant enrichment or biases) of the main gene clusters. 7C: Potential regulatory interactions of broad cellular functionality via the energetic status of the cell, reflected, e.g., in ATP:ADP ratios. In the oxidative phase catabolic activity leads to a high ATP synthesis rate. At high ATP:ADP ratios promoters of anabolic genes are active, potentially mediated by ATP-dependent nucleosome remodeling, which at the same time keeps promoters of catabolic genes in a repressed state. When respiratory activity suddenly slows down in the reductive phase the activity of the anabolic genes, i.e., amino acid and protein synthesis, leads to a decrease of the ATP:ADP ratio and the promoters of catabolic genes become active. Diverse cellular stresses may result in a sudden drop in the cellular ATP:ADP ratio due to the energetic costs of immediate biochemical stress response.

Mentions: In this work, we have identified seven consensus clusters of genes, whose transcripts show periodic time-series during both, the 0.7 h [11] and the 5 h [10] period respiratory oscillations. Specifically, clusters A, AB, B, C and D define a common temporal gene expression program (Figures 1 & 7A). Their relation to respiratory activity and their functional enrichment profiles (Tables 1, S3 & S4) support a distinction of two superclusters. The cell growth supercluster (AABB) is expressed during the oxidative phase, and the energy-mobilizing supercluster (CD) is expressed in the reductive phase. Each supercluster develops from predominantly TATA-less and TFIID-controlled genes that encode for ribosome biogenesis (A/AB: cytoplasmic or C: mitochondrial), to gene groups that are enriched in TATA Boxes and SAGA-control and encode for metabolic functions (B: amino acid synthesis or D: catabolism and stress-response) (Figure 7B).


The yin and yang of yeast transcription: elements of a global feedback system between metabolism and chromatin.

Machné R, Murray DB - PLoS ONE (2012)

Summary of results & proposed feedback model.7A: temporal flow of expression and functional relationships of cluster transcripts in the 0.7 h system (left to right) and the 5 h system (top to bottom). 7B: summary of observed properties (significant enrichment or biases) of the main gene clusters. 7C: Potential regulatory interactions of broad cellular functionality via the energetic status of the cell, reflected, e.g., in ATP:ADP ratios. In the oxidative phase catabolic activity leads to a high ATP synthesis rate. At high ATP:ADP ratios promoters of anabolic genes are active, potentially mediated by ATP-dependent nucleosome remodeling, which at the same time keeps promoters of catabolic genes in a repressed state. When respiratory activity suddenly slows down in the reductive phase the activity of the anabolic genes, i.e., amino acid and protein synthesis, leads to a decrease of the ATP:ADP ratio and the promoters of catabolic genes become active. Diverse cellular stresses may result in a sudden drop in the cellular ATP:ADP ratio due to the energetic costs of immediate biochemical stress response.
© Copyright Policy
Related In: Results  -  Collection

Show All Figures
getmorefigures.php?uid=PMC3369881&req=5

pone-0037906-g007: Summary of results & proposed feedback model.7A: temporal flow of expression and functional relationships of cluster transcripts in the 0.7 h system (left to right) and the 5 h system (top to bottom). 7B: summary of observed properties (significant enrichment or biases) of the main gene clusters. 7C: Potential regulatory interactions of broad cellular functionality via the energetic status of the cell, reflected, e.g., in ATP:ADP ratios. In the oxidative phase catabolic activity leads to a high ATP synthesis rate. At high ATP:ADP ratios promoters of anabolic genes are active, potentially mediated by ATP-dependent nucleosome remodeling, which at the same time keeps promoters of catabolic genes in a repressed state. When respiratory activity suddenly slows down in the reductive phase the activity of the anabolic genes, i.e., amino acid and protein synthesis, leads to a decrease of the ATP:ADP ratio and the promoters of catabolic genes become active. Diverse cellular stresses may result in a sudden drop in the cellular ATP:ADP ratio due to the energetic costs of immediate biochemical stress response.
Mentions: In this work, we have identified seven consensus clusters of genes, whose transcripts show periodic time-series during both, the 0.7 h [11] and the 5 h [10] period respiratory oscillations. Specifically, clusters A, AB, B, C and D define a common temporal gene expression program (Figures 1 & 7A). Their relation to respiratory activity and their functional enrichment profiles (Tables 1, S3 & S4) support a distinction of two superclusters. The cell growth supercluster (AABB) is expressed during the oxidative phase, and the energy-mobilizing supercluster (CD) is expressed in the reductive phase. Each supercluster develops from predominantly TATA-less and TFIID-controlled genes that encode for ribosome biogenesis (A/AB: cytoplasmic or C: mitochondrial), to gene groups that are enriched in TATA Boxes and SAGA-control and encode for metabolic functions (B: amino acid synthesis or D: catabolism and stress-response) (Figure 7B).

Bottom Line: We show that the ATP:ADP ratio oscillates, compatible with alternating metabolic activity of the two superclusters and differential feedback on their transcription via activating (RSC) and repressive (Isw2) types of promoter structure remodeling.We propose a novel feedback mechanism, where the energetic state of the cell, reflected in the ATP:ADP ratio, gates the transcription of large, but functionally coherent groups of genes via differential effects of ATP-dependent nucleosome remodeling machineries.Besides providing a mechanistic hypothesis for the delayed negative feedback that results in the oscillatory phenotype, this mechanism may underpin the continuous adaptation of growth to environmental conditions.

View Article: PubMed Central - PubMed

Affiliation: Institute for Theoretical Chemistry, University of Vienna, Vienna, Austria. raim@tbi.univie.ac.at

ABSTRACT
When grown in continuous culture, budding yeast cells tend to synchronize their respiratory activity to form a stable oscillation that percolates throughout cellular physiology and involves the majority of the protein-coding transcriptome. Oscillations in batch culture and at single cell level support the idea that these dynamics constitute a general growth principle. The precise molecular mechanisms and biological functions of the oscillation remain elusive. Fourier analysis of transcriptome time series datasets from two different oscillation periods (0.7 h and 5 h) reveals seven distinct co-expression clusters common to both systems (34% of all yeast ORF), which consolidate into two superclusters when correlated with a compilation of 1,327 unrelated transcriptome datasets. These superclusters encode for cell growth and anabolism during the phase of high, and mitochondrial growth, catabolism and stress response during the phase of low oxygen uptake. The promoters of each cluster are characterized by different nucleotide contents, promoter nucleosome configurations, and dependence on ATP-dependent nucleosome remodeling complexes. We show that the ATP:ADP ratio oscillates, compatible with alternating metabolic activity of the two superclusters and differential feedback on their transcription via activating (RSC) and repressive (Isw2) types of promoter structure remodeling. We propose a novel feedback mechanism, where the energetic state of the cell, reflected in the ATP:ADP ratio, gates the transcription of large, but functionally coherent groups of genes via differential effects of ATP-dependent nucleosome remodeling machineries. Besides providing a mechanistic hypothesis for the delayed negative feedback that results in the oscillatory phenotype, this mechanism may underpin the continuous adaptation of growth to environmental conditions.

Show MeSH
Related in: MedlinePlus