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 in silico 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 lac 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.
