The Ability of Feed-Forward Regulatory Loops to Adapt: Dependence on Model Parameters and Conditions of Absolute Adaptation

Abstract

Feed-forward regulatory loops, where a transcription factor (TF) regulates target gene expression in two ways, directly and through a microRNA (miRNA), are widely involved in gene networks. A feed-forward regulatory loop is termed coherent when its regulatory branches exert similar effects on the target gene and incoherent otherwise. The objective of the study was to understand whether feed-forward regulatory loops are capable of adapting to changes in the number of TF molecules. Two coherent and two incoherent loops were considered using two different models involving different regulatory mechanisms. Coherent loops were found to be incapable of adaptation in contrast to incoherent loops, which demonstrated perfect adaptation within specific parameter sets; i.e., target gene expression was insensitive to variation in TF number. Adaptation of incoherent loops was observed to occur only when a sufficient number of miRNA molecules are available in the system.