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Balancing noise and plasticity in eukaryotic gene expression.

Bajić D, Poyatos JF - BMC Genomics (2012)

Bottom Line: This additionally implies that genome neighboring organization -as modifier- appears only effective in highly plastic genes.In this class, we confirm bidirectional promoters (bipromoters) as a configuration capable to reduce coupling by abating noise but also reveal an important trade-off, since bipromoters also decrease plasticity.This presents ultimately a paradox between intergenic distances and modulation, with short intergenic distances both associated and disassociated to noise at different plasticity levels.

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Affiliation: Logic of Genomic Systems Laboratory, Spanish National Biotechnology Centre, Consejo Superior de Investigaciones Científicas-CSIC, Madrid, Spain. jpoyatos@cnb.csic.es

ABSTRACT

Background: Coupling the control of expression stochasticity (noise) to the ability of expression change (plasticity) can alter gene function and influence adaptation. A number of factors, such as transcription re-initiation, strong chromatin regulation or genome neighboring organization, underlie this coupling. However, these factors do not necessarily combine in equivalent ways and strengths in all genes. Can we identify then alternative architectures that modulate in distinct ways the linkage of noise and plasticity?

Results: Here we first show that strong chromatin regulation, commonly viewed as a source of coupling, can lead to plasticity without noise. The nature of this regulation is relevant too, with plastic but noiseless genes being subjected to general activators whereas plastic and noisy genes experience more specific repression. Contrarily, in genes exhibiting poor transcriptional control, it is translational efficiency what separates noise from plasticity, a pattern related to transcript length. This additionally implies that genome neighboring organization -as modifier- appears only effective in highly plastic genes. In this class, we confirm bidirectional promoters (bipromoters) as a configuration capable to reduce coupling by abating noise but also reveal an important trade-off, since bipromoters also decrease plasticity. This presents ultimately a paradox between intergenic distances and modulation, with short intergenic distances both associated and disassociated to noise at different plasticity levels.

Conclusions: Balancing the coupling among different types of expression variability appears as a potential shaping force of genome regulation and organization. This is reflected in the use of different control strategies at genes with different sets of functional constraints.

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Noise plasticity coupling is modulated by genomic neighborhood and distinguishes four control strategies overall.A). A cartoon depicting the different genomic structures (bipromoter, parallel, divergent) upstream of coding genes is shown in ascending order of proximal nucleosome occupancy, plasticity and noise (which coincide). For each structure, we show the average intergenic distance in blue. In red is shown the Spearman ρcoefficient for the observed noise-plasticity correlation. We also show the percent within each class of a given upstream structure , e.g., HNHP mostly exhibit parallel/divergent coding (C) and divergent non-coding (NC) transcripts. B) Four regulatory strategies broadly adjust the noise-plasticity coupling. These strategies emphasize the alternative transcriptional- or translational-based modes of balancing noise and plasticity in yeast.
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Figure 5: Noise plasticity coupling is modulated by genomic neighborhood and distinguishes four control strategies overall.A). A cartoon depicting the different genomic structures (bipromoter, parallel, divergent) upstream of coding genes is shown in ascending order of proximal nucleosome occupancy, plasticity and noise (which coincide). For each structure, we show the average intergenic distance in blue. In red is shown the Spearman ρcoefficient for the observed noise-plasticity correlation. We also show the percent within each class of a given upstream structure , e.g., HNHP mostly exhibit parallel/divergent coding (C) and divergent non-coding (NC) transcripts. B) Four regulatory strategies broadly adjust the noise-plasticity coupling. These strategies emphasize the alternative transcriptional- or translational-based modes of balancing noise and plasticity in yeast.

Mentions: The above can be complementary analyzed if we consider all possible local genomic architectures around a focal gene (Figure5A), i.e., parallel, divergent and bipromoters with a coding or non-coding transcript as upstream partner (noncoding partners include “cryptic unstable transcripts”, CUTs, and “stable untranslated transcripts”, SUTs, see[30] and Methods; bipromoters CUTS were recently associated with low noise[16]). We computed the coupling between noise and plasticity for each architecture. Coupling is strong for genes with divergent transcripts (independent of the type of upstream partner) and weak for those with a bipromoter with a coding partner (Figure5A). This further validates the observed absence of bipromoters in HNHP genes and their enrichment in the other three classes (bipromoters are the most commonly found architecture in LNLP, HNLP and LNHP) where they are associated, of course, to short intergenic distances (Figure5A, see also Additional file1: Figure S10). Interestingly, bipromoters of plastic genes with low noise are the ones with the biggest (relative) intergenic distance (with respect to LNLP and HNLP), which suggests again the requirement of a minimal distance to locate the regulatory demands associated to enhance plasticity (mean distance bipromoters of LNHP: 252 bp, in the LNLP and HNLP groups: 178bp, p = 1.1 × 10−3, Wilcoxon test). Overall, this emphasizes bipromoters as noise-abating architecture only when noise and plasticity are transcriptionally modulated.


Balancing noise and plasticity in eukaryotic gene expression.

Bajić D, Poyatos JF - BMC Genomics (2012)

Noise plasticity coupling is modulated by genomic neighborhood and distinguishes four control strategies overall.A). A cartoon depicting the different genomic structures (bipromoter, parallel, divergent) upstream of coding genes is shown in ascending order of proximal nucleosome occupancy, plasticity and noise (which coincide). For each structure, we show the average intergenic distance in blue. In red is shown the Spearman ρcoefficient for the observed noise-plasticity correlation. We also show the percent within each class of a given upstream structure , e.g., HNHP mostly exhibit parallel/divergent coding (C) and divergent non-coding (NC) transcripts. B) Four regulatory strategies broadly adjust the noise-plasticity coupling. These strategies emphasize the alternative transcriptional- or translational-based modes of balancing noise and plasticity in yeast.
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC3539894&req=5

Figure 5: Noise plasticity coupling is modulated by genomic neighborhood and distinguishes four control strategies overall.A). A cartoon depicting the different genomic structures (bipromoter, parallel, divergent) upstream of coding genes is shown in ascending order of proximal nucleosome occupancy, plasticity and noise (which coincide). For each structure, we show the average intergenic distance in blue. In red is shown the Spearman ρcoefficient for the observed noise-plasticity correlation. We also show the percent within each class of a given upstream structure , e.g., HNHP mostly exhibit parallel/divergent coding (C) and divergent non-coding (NC) transcripts. B) Four regulatory strategies broadly adjust the noise-plasticity coupling. These strategies emphasize the alternative transcriptional- or translational-based modes of balancing noise and plasticity in yeast.
Mentions: The above can be complementary analyzed if we consider all possible local genomic architectures around a focal gene (Figure5A), i.e., parallel, divergent and bipromoters with a coding or non-coding transcript as upstream partner (noncoding partners include “cryptic unstable transcripts”, CUTs, and “stable untranslated transcripts”, SUTs, see[30] and Methods; bipromoters CUTS were recently associated with low noise[16]). We computed the coupling between noise and plasticity for each architecture. Coupling is strong for genes with divergent transcripts (independent of the type of upstream partner) and weak for those with a bipromoter with a coding partner (Figure5A). This further validates the observed absence of bipromoters in HNHP genes and their enrichment in the other three classes (bipromoters are the most commonly found architecture in LNLP, HNLP and LNHP) where they are associated, of course, to short intergenic distances (Figure5A, see also Additional file1: Figure S10). Interestingly, bipromoters of plastic genes with low noise are the ones with the biggest (relative) intergenic distance (with respect to LNLP and HNLP), which suggests again the requirement of a minimal distance to locate the regulatory demands associated to enhance plasticity (mean distance bipromoters of LNHP: 252 bp, in the LNLP and HNLP groups: 178bp, p = 1.1 × 10−3, Wilcoxon test). Overall, this emphasizes bipromoters as noise-abating architecture only when noise and plasticity are transcriptionally modulated.

Bottom Line: This additionally implies that genome neighboring organization -as modifier- appears only effective in highly plastic genes.In this class, we confirm bidirectional promoters (bipromoters) as a configuration capable to reduce coupling by abating noise but also reveal an important trade-off, since bipromoters also decrease plasticity.This presents ultimately a paradox between intergenic distances and modulation, with short intergenic distances both associated and disassociated to noise at different plasticity levels.

View Article: PubMed Central - HTML - PubMed

Affiliation: Logic of Genomic Systems Laboratory, Spanish National Biotechnology Centre, Consejo Superior de Investigaciones Científicas-CSIC, Madrid, Spain. jpoyatos@cnb.csic.es

ABSTRACT

Background: Coupling the control of expression stochasticity (noise) to the ability of expression change (plasticity) can alter gene function and influence adaptation. A number of factors, such as transcription re-initiation, strong chromatin regulation or genome neighboring organization, underlie this coupling. However, these factors do not necessarily combine in equivalent ways and strengths in all genes. Can we identify then alternative architectures that modulate in distinct ways the linkage of noise and plasticity?

Results: Here we first show that strong chromatin regulation, commonly viewed as a source of coupling, can lead to plasticity without noise. The nature of this regulation is relevant too, with plastic but noiseless genes being subjected to general activators whereas plastic and noisy genes experience more specific repression. Contrarily, in genes exhibiting poor transcriptional control, it is translational efficiency what separates noise from plasticity, a pattern related to transcript length. This additionally implies that genome neighboring organization -as modifier- appears only effective in highly plastic genes. In this class, we confirm bidirectional promoters (bipromoters) as a configuration capable to reduce coupling by abating noise but also reveal an important trade-off, since bipromoters also decrease plasticity. This presents ultimately a paradox between intergenic distances and modulation, with short intergenic distances both associated and disassociated to noise at different plasticity levels.

Conclusions: Balancing the coupling among different types of expression variability appears as a potential shaping force of genome regulation and organization. This is reflected in the use of different control strategies at genes with different sets of functional constraints.

Show MeSH