The gene expression cascade leading to the lysogenic pathway also starts with divergent transcription initiated from the PL and PR promoters. However, the accumulation of the CII regulator prevents the expression of the lytic regulators. The CII regulator is a tetramer. Each of the four monomers has a helix-turn-helix motif. However, only two of these motifs bind to DNA. The function of the other two motifs is not known.
The CII regulator activates transcription initiated from PRE, PI, and PaQ. Activation of PRE leads to rapid CI regulator synthesis. The CI regulator that accumulates in response to this activation binds to OL and OR and represses transcription from the early promoters PL and PR. The structure of the CI regulator protein and its interaction with operator DNA is described below. The intracellular concentration of the CI regulator that accumulates in response to the activation at PRE is 10 to 20 times higher than that present in an established λ lysogen. The initial high concentration of the CI regulator probably ensures that all infecting phage DNA becomes repressed. Activation from P1, stimulates transcription of the int gene. The product of this gene, integrase, is needed to insert λ DNA into the host chromosome to form the prophage. The PaQ promoter is located within the Q gene. Therefore, the CII regulator inhibits transcription of the Q gene when it binds to this promoter. Furthermore, the PaQ transcript appears to function as an antisense RNA that inhibits the translation of the Q transcript. As should now be clear the CII protein is very important for establishing lysogeny. An ATP-dependent host protein called FtsH can prevent the infected cell from entering the lysogenic pathway by cleaving CII. The CIII protein prevents this from happening by inhibiting the FtsH protease.