Anticipating response function in gene regulatory networks.

Abstract

The origin of an ordered genetic response of a complex and noisy biological cell is intimately related to the detailed mechanism of protein-DNA interactions present in a wide variety of gene regulatory (GR) systems. However, the quantitative prediction of genetic response and the correlation between the mechanism and the response curve is poorly understood. Here, we report <i>in silico</i> binding studies of GR systems to show that the transcription factor (TF) binds to multiple DNA sites with high cooperativity spreads from specific binding sites into adjacent non-specific DNA and bends the DNA. Our analysis is not limited only to the isolated model system but also can be applied to a system containing multiple interacting genes. The controlling role of TF oligomerization, TF-ligand interactions, and DNA looping for gene expression has been also characterized. The predictions are validated against detailed grand canonical Monte Carlo simulations and published data for the <i>lac</i> operon system. Overall, our study reveals that the expression of target genes can be quantitatively controlled by modulating TF-ligand interactions and the bending energy of DNA.