Bajic D, Poyatos JF.
Coupling the control of expression stochasticity (noise) with the ability of expression change (plasticity) can constrain gene function and limit adaptation. Several factors, such as transcription re-initiation, strong chromatin regulation or genome neighboring organization, underlie this coupling. However, neither the same combination of these mechanisms nor their specific strength act equally in all genes. Can we identify alternative architectures that modulate in distinct ways the coupling between noise and plasticity?
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 also relevant, with plastic but noiseless genes being subjected to broad expression activation whereas plastic and noisy genes experience more specific forms of repression. Contrarily, in genes exhibiting poor transcriptional control, it is translational efficiency what separates noise from plasticity, a pattern linked to transcript length. This also implies that neighboring genome architecture as modifier appears only effective in highly plastic genes. In this class, we confirm bipromoters as an architecture capable to reduce coupling (by reducing noise) but also uncover an important trade-off, as they 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.
Balancing the coupling among different types of expression variability appears as a potential shaping force of genome architecture. This is reflected in the use of different regulatory strategies at genes with different sets of functional constraints.