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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.

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Dual action of histones. Both trans-acting chromatin regulators and histones tend to have opposite effects in HNHP and LNHP genes. For each mutation from[18], we plot the fraction of genes in the HNHP group and in the LNHP group that decreased expression. Consistently with that observed in Figure2, we find that mutating as much as ∼50% of chromatin regulators results in the de-activation of the majority of the LNHP genes, but de-repression of most of the HNHP genes. In addition, and perhaps more importantly, we observe that 81% of mutations in histones also exhibit this behavior. This is probably crucial, and indicates that histones by themselves are needed for repression of HNHP genes and, at the same time, activation of LNHP.
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Figure 3: Dual action of histones. Both trans-acting chromatin regulators and histones tend to have opposite effects in HNHP and LNHP genes. For each mutation from[18], we plot the fraction of genes in the HNHP group and in the LNHP group that decreased expression. Consistently with that observed in Figure2, we find that mutating as much as ∼50% of chromatin regulators results in the de-activation of the majority of the LNHP genes, but de-repression of most of the HNHP genes. In addition, and perhaps more importantly, we observe that 81% of mutations in histones also exhibit this behavior. This is probably crucial, and indicates that histones by themselves are needed for repression of HNHP genes and, at the same time, activation of LNHP.

Mentions: We also found that some regulators whose deletion results in decreasing expression level in the majority of LNHP genes tends in comparison to increase it in the majority of HNHP (Figure3). As expected, this is not related to general transcription factors, whose deletion reduce expression level, but to many specific chromatin regulators and, notably, to histones. As much as 81% of these histone deletions (see also Additional file1: Figure S7) caused an increase in the expression of most HNHP genes, while they decreased the expression level of the majority of LNHP. A recent result can help us understand this[13]. Namely, LNHP genes are greatly enriched in activating marks (mostly acetylations), a strong change in acetylation level being observed when repressed. Therefore, acetylated histones are probably essential for the expression of these genes. On the contrary, HNHP genes do not show such changes in histone acetylation status, but they reduce their occupancy level when activated. Histone deletion is in this case more likely to impede the formation of repressive nucleosomes, resulting in a more frequently open promoter and increasing expression level (see Additional file1: Supplement for more discussion, and Additional file1: Figure S8 for a detailed profile of histone modifications).


Balancing noise and plasticity in eukaryotic gene expression.

Bajić D, Poyatos JF - BMC Genomics (2012)

Dual action of histones. Both trans-acting chromatin regulators and histones tend to have opposite effects in HNHP and LNHP genes. For each mutation from[18], we plot the fraction of genes in the HNHP group and in the LNHP group that decreased expression. Consistently with that observed in Figure2, we find that mutating as much as ∼50% of chromatin regulators results in the de-activation of the majority of the LNHP genes, but de-repression of most of the HNHP genes. In addition, and perhaps more importantly, we observe that 81% of mutations in histones also exhibit this behavior. This is probably crucial, and indicates that histones by themselves are needed for repression of HNHP genes and, at the same time, activation of LNHP.
© Copyright Policy - open-access
Related In: Results  -  Collection

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

Figure 3: Dual action of histones. Both trans-acting chromatin regulators and histones tend to have opposite effects in HNHP and LNHP genes. For each mutation from[18], we plot the fraction of genes in the HNHP group and in the LNHP group that decreased expression. Consistently with that observed in Figure2, we find that mutating as much as ∼50% of chromatin regulators results in the de-activation of the majority of the LNHP genes, but de-repression of most of the HNHP genes. In addition, and perhaps more importantly, we observe that 81% of mutations in histones also exhibit this behavior. This is probably crucial, and indicates that histones by themselves are needed for repression of HNHP genes and, at the same time, activation of LNHP.
Mentions: We also found that some regulators whose deletion results in decreasing expression level in the majority of LNHP genes tends in comparison to increase it in the majority of HNHP (Figure3). As expected, this is not related to general transcription factors, whose deletion reduce expression level, but to many specific chromatin regulators and, notably, to histones. As much as 81% of these histone deletions (see also Additional file1: Figure S7) caused an increase in the expression of most HNHP genes, while they decreased the expression level of the majority of LNHP. A recent result can help us understand this[13]. Namely, LNHP genes are greatly enriched in activating marks (mostly acetylations), a strong change in acetylation level being observed when repressed. Therefore, acetylated histones are probably essential for the expression of these genes. On the contrary, HNHP genes do not show such changes in histone acetylation status, but they reduce their occupancy level when activated. Histone deletion is in this case more likely to impede the formation of repressive nucleosomes, resulting in a more frequently open promoter and increasing expression level (see Additional file1: Supplement for more discussion, and Additional file1: Figure S8 for a detailed profile of histone modifications).

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