Negative DNA supercoiling tunes protein-mediated looping

Protein-mediated DNA looping is fundamental to gene regulation. Such loops occur stochastically in purified systems, but additional proteins and/or DNA supercoiling might tune looping for definitive responses. In lac repressor-mediated looping, the probabilities of loops in individual molecules ranged 0-100, and individual molecules exhibited representative behavior only in observations lasting an hour or more. Titrating with HU protein progressively compacted the DNA and increased the average probability of looping without narrowing the 0-100 distribution. Increased negative supercoiling also raised the average looping probability for the ensemble of molecules as well, but individual molecules more closely resembled the average. Furthermore, in only twelve minutes of observation, well within the shortest doubling time of the bacterium, most molecules exhibited the looping probability of the ensemble. DNA supercoiling, an inherent feature of all genomes, appears to be a fundamental determinant of time-constrained, emergent behavior in otherwise random molecular activity.