Schubert, R.Dodd, I.Egan, J.Shearwin, K.2008-05-072008-05-072007Genes & Development, 2007; 21(19):2461-24720890-93691549-5477http://hdl.handle.net/2440/43419CI represses cro; Cro represses cI. This double negative feedback loop is the core of the classical CI-Cro epigenetic switch of bacteriophage lambda. Despite the classical status of this switch, the role in lambda development of Cro repression of the P(RM) promoter for CI has remained unclear. To address this, we created binding site mutations that strongly impaired Cro repression of P(RM) with only minimal effects on CI regulation of P(RM). These mutations had little impact on lambda development after infection but strongly inhibited the transition from lysogeny to the lytic pathway. We demonstrate that following inactivation of CI by ultraviolet treatment of lysogens, repression of P(RM) by Cro is needed to prevent synthesis of new CI that would otherwise significantly impede lytic development. Thus a bistable CI-Cro circuit reinforces the commitment to a developmental transition.enCopyright © 2007 by Cold Spring Harbor Laboratory Press.Bacteriophage lambdaProphagesDNA-Binding ProteinsRepressor ProteinsLysogenyVirus ActivationGene Expression Regulation, ViralBase SequenceMutationMolecular Sequence DataViral Regulatory and Accessory ProteinsPromoter Regions, GeneticJournal article002007283510.1101/gad.15849070002500622000082-s2.0-3494887466447422Dodd, I. [0000-0003-2969-6841]Shearwin, K. [0000-0002-7736-2742]