  Bacterial genomes have been shown to be partitioned into several kilobases
long chromosomal domains that are topologically independent from each other,
meaning that change of DNA superhelicity in one domain does not propagate to
neighbors. Both in vivo and in vitro experiments have been performed to
question the nature of the topological barriers at play, leading to several
predictions on possible molecular actors. Here, we address the question of
topological barriers using polymer models of supercoiled DNA chains. More
specifically, we determine under which conditions DNA-bridging proteins may act
as topological barriers. To this end, we developed a coarse-grained
bead-and-spring model and investigated its properties through Brownian dynamics
simulations. As a result, we find that DNA-bridging proteins must exert rather
strong constraints on their binding sites: they must block the diffusion of the
excess of twist through the two binding sites on the DNA molecule and,
simultaneously, prevent the rotation of one DNA segment relative to the other
one. Importantly, not all DNA-bridging proteins satisfy this second condition.
For example, single bridges formed by proteins that bind DNA non-specifically,
like H-NS dimers, are expected to fail with this respect. Our findings might
also explain, in the case of specific DNA-bridging proteins like LacI, why
multiple bridges are required to create stable independent topological domains.
Strikingly, when the relative rotation of the DNA segments is not prevented,
relaxation results in complex intrication of the two domains. Moreover, while
the value of the torsional stress in each domain may vary, their differential
is preserved. Our work also predicts that nucleoid associated proteins known to
wrap DNA must form higher protein-DNA complexes to efficiently work as
topological barriers.
