The
integration host factor (IHF) is a prominent example of indirect readout as it imposes one of the strongest
bends on relaxed linear
DNA. However, the relation between IHF and torsionally constrained
DNA, as occurs physiologically, remains unclear. By using atomistic molecular dynamics simulations on
DNA minicircles, we reveal, for the first time, the reciprocal influence between
a DNA-bending
protein and supercoiling. On one hand, the increased curvature of
supercoiled DNA enhances wrapping around IHF making the final complex topologically dependent. On the other hand, IHF acts as a 'supercoiling relief' factor by compacting relaxed
DNA loops and, when supercoiled, it pins the position of plectonemes in a unique and specific manner. In addition, IHF restrains under- or overtwisted
DNA depending on whether the complex is formed in negatively or positively
supercoiled DNA, becoming effectively a 'supercoiling
buffer'. We finally provide evidence of
DNA bridging by IHF and reveal that these bridges divide
DNA into independent topological domains. We anticipate that the crosstalk detected here between the 'active'
DNA and the multifaceted IHF could be common to other
DNA-
protein complexes relying on the deformation of
DNA.