Cro’s role in the CI–Cro bistable switch is critical for λ’s transition from lysogeny to lytic development

Abstract

CI represses cro; Cro represses cI. This double negative feedback loop is the core of the classical CI–Cro epigenetic switch of bacteriophage λ. Despite the classical status of this switch, the role in λ 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 λ 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.

Keywords

• Bistability
• epigenetic
• bacteriophage λ
• genetic switch
• Cro
• transcriptional control