Figure 1 Loop conformations and the in vivo free energy of DNA looping by the lac repressor. From [5]

It has been accounted in a previous paper [1-4] that different relative distance of the two operators can cause a periodic fluctuation in co-repression intensity. The reason is that when the two operators are a certain number of nucleotides apart, the Lac Repressor dimer tend to tetramerize and further lead to a partial supercoiling of the DNA, as is shown in the figure.

Such a partial supercoiling will hinder the binding of the RNA Polymerase to DNA, thus practicing a much stronger repression than a single repressor does. Since the partial supercoiling forms in periodicity according to the different relative distance of the two operators, the co-repression intensity there-caused presents periodicity as well.


  1. Y Flashner and J D Gralla, Dual Mechanism of Repression at a Distance in the lac Operon. PNAS. 1988 Dec;85(23):8968–8972.
  2. Saiz, L., Rubi, J.M. & Vilar, J.M.G. Inferring the in vivo looping properties of DNA. PNAS. 102, 17642-5 (2005).
  3. Swigon, D., Coleman, B.D. & Olson, W.K. Modeling the Lac repressor-operator assembly: The influence of DNA looping on Lac repressor conformation. PNAS 103, 9879-9884 (2006).
  4. Müller, J., Oehler, S. & Müller-Hill, B. Repression of lac promoter as a function of distance, phase and quality of an auxiliary lac operator. J. Mol. Bio. 257, 21-9 (1996).
  5. Saiz, L. & Vilar, J. M. G. (2006), DNA looping: the consequences and its control., Curr Opin Struct Biol 16(3), 344--350.