In vivo non-specific binding of lambda CI and Cro repressors is significant.

We propose a thermodynamic model that includes the non-specific binding of the lambda phage regulatory proteins CI and Cro. By fitting the model to experimental in vivo data on activities of the two promoters P(RM) and P(R) versus concentration, we estimate the free energy upon non-specific binding to be -4.1+/-0.9 kcal/mol for CI and -4.2+/-0.8 kcal/mol for Cro. For concentrations >100 nM of CI or Cro, we find that >50% of these proteins are non-specifically bound. In particular, in a lysogen (approximately 250 CI monomeric equivalents per cell) nearly 90% of CI is non-specifically bound.