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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.

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
Proximal nucleosomal occupancy, chromatin regulation, and the noise-plasticity coupling. We divided the dataset (n = 2045) in ten equally sized bins of increasing proximal nucleosome occupancy. In each bin, we computed the median chromatin regulation effect (CRE). We plotted the difference in plasticity (A, blue curve) or noise (B, red curve) of genes above/below this median and contrasted the observed values with those expected randomly (permutation test in each bin to depict significance, shown as the mean –gray curve– and mean plus two standard deviations –dashed gray curves– obtained with 10000 randomizations). Plasticity is always enhanced by strong chromatin regulation; however, regulation enhances noise only in promoters with high proximal nucleosome occupancy and TATA box (shaded area in A,B). An identical analysis is shown in (C) and (D), but excluding genes with TATA-containing promoters. High occupancy does not lead to increased plasticity/noise in this case (shaded area in C,D).
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Figure 1: Proximal nucleosomal occupancy, chromatin regulation, and the noise-plasticity coupling. We divided the dataset (n = 2045) in ten equally sized bins of increasing proximal nucleosome occupancy. In each bin, we computed the median chromatin regulation effect (CRE). We plotted the difference in plasticity (A, blue curve) or noise (B, red curve) of genes above/below this median and contrasted the observed values with those expected randomly (permutation test in each bin to depict significance, shown as the mean –gray curve– and mean plus two standard deviations –dashed gray curves– obtained with 10000 randomizations). Plasticity is always enhanced by strong chromatin regulation; however, regulation enhances noise only in promoters with high proximal nucleosome occupancy and TATA box (shaded area in A,B). An identical analysis is shown in (C) and (D), but excluding genes with TATA-containing promoters. High occupancy does not lead to increased plasticity/noise in this case (shaded area in C,D).

Mentions: To better understand how such factors determine the noise-plasticity coupling, we used a score that assesses chromatin regulation effects (CRE), i.e., how much the expression of a given gene varies when deleting its trans-acting chromatin regulators[8-10,18] (Methods). CRE correlated with plasticity as expected (Spearman’s correlation coefficient ρ = 0.57,p < 10−20, n = 2045). We then grouped genes in terms of proximal nucleosome occupancy and computed mean plasticity for those genes exhibiting high or low CRE within each group. Notably, chromatin regulation can induce a relatively high level of plasticity independent of nucleosomal occupancy and presence of TATA promoters (Figure1). Is it possible to identify genes with particularly strong plasticity? This distinguishes genes whose promoters present both high proximal nucleosomal occupancy –increasing sensitivity to regulation (Additional file1: Figure S1)[10]– and presence of TATA box –that results in bursting transcription and increased transcriptional efficiency[5]– which in turn involves coupling to noise (confirming earlier reports[3,8], Additional file1: Figure S2).


Balancing noise and plasticity in eukaryotic gene expression.

Bajić D, Poyatos JF - BMC Genomics (2012)

Proximal nucleosomal occupancy, chromatin regulation, and the noise-plasticity coupling. We divided the dataset (n = 2045) in ten equally sized bins of increasing proximal nucleosome occupancy. In each bin, we computed the median chromatin regulation effect (CRE). We plotted the difference in plasticity (A, blue curve) or noise (B, red curve) of genes above/below this median and contrasted the observed values with those expected randomly (permutation test in each bin to depict significance, shown as the mean –gray curve– and mean plus two standard deviations –dashed gray curves– obtained with 10000 randomizations). Plasticity is always enhanced by strong chromatin regulation; however, regulation enhances noise only in promoters with high proximal nucleosome occupancy and TATA box (shaded area in A,B). An identical analysis is shown in (C) and (D), but excluding genes with TATA-containing promoters. High occupancy does not lead to increased plasticity/noise in this case (shaded area in C,D).
© Copyright Policy - open-access
Related In: Results  -  Collection

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

Figure 1: Proximal nucleosomal occupancy, chromatin regulation, and the noise-plasticity coupling. We divided the dataset (n = 2045) in ten equally sized bins of increasing proximal nucleosome occupancy. In each bin, we computed the median chromatin regulation effect (CRE). We plotted the difference in plasticity (A, blue curve) or noise (B, red curve) of genes above/below this median and contrasted the observed values with those expected randomly (permutation test in each bin to depict significance, shown as the mean –gray curve– and mean plus two standard deviations –dashed gray curves– obtained with 10000 randomizations). Plasticity is always enhanced by strong chromatin regulation; however, regulation enhances noise only in promoters with high proximal nucleosome occupancy and TATA box (shaded area in A,B). An identical analysis is shown in (C) and (D), but excluding genes with TATA-containing promoters. High occupancy does not lead to increased plasticity/noise in this case (shaded area in C,D).
Mentions: To better understand how such factors determine the noise-plasticity coupling, we used a score that assesses chromatin regulation effects (CRE), i.e., how much the expression of a given gene varies when deleting its trans-acting chromatin regulators[8-10,18] (Methods). CRE correlated with plasticity as expected (Spearman’s correlation coefficient ρ = 0.57,p < 10−20, n = 2045). We then grouped genes in terms of proximal nucleosome occupancy and computed mean plasticity for those genes exhibiting high or low CRE within each group. Notably, chromatin regulation can induce a relatively high level of plasticity independent of nucleosomal occupancy and presence of TATA promoters (Figure1). Is it possible to identify genes with particularly strong plasticity? This distinguishes genes whose promoters present both high proximal nucleosomal occupancy –increasing sensitivity to regulation (Additional file1: Figure S1)[10]– and presence of TATA box –that results in bursting transcription and increased transcriptional efficiency[5]– which in turn involves coupling to noise (confirming earlier reports[3,8], Additional file1: Figure S2).

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