Cooperativity in long-range gene regulation by the λ CI repressor

By Ian B. Dodd, K. Shearwin, Alison J. Perkins, Tom Burr, A. Hochschild, J. Egan. 2004

169 citations recorded by the source corpus.

Effective repression of cI transcription from PRM by the bacteriophage λ CI repressor requires binding sites (OL) located 2.4 kb from the promoter. A CI tetramer bound to OL1.OL2 interacts with a tetramer bound near PRM (OR1.OR2), looping the intervening DNA. We previously proposed that in this CI octamer:DNA complex, the distant OL3 operator and the weak OR3 operator overlapping PRM are juxtaposed so that a CI dimer at OL3 can cooperate with a CI dimer binding to OR3. Here we show that OL3 is necessary for effective repression of PRM and that the repressor at OL3 appears to interact specifically with the repressor at OR3. The OL3-CI-OR3 interaction involves the same CI interface used for short-range dimer-dimer interactions and does not occur without the other four operators. The long-range interactions were incorporated into a physicochemical model, allowing estimation of the long-range interaction energies and showing the lysogenic state to be ideally poised for CI negative autoregulation. The results establish the λ system as a powerful tool for examining long-range gene regulatory interactions in vivo.

Subfields: Genetics, Molecular Biology

View Paper: https://www.semanticscholar.org/paper/52e68d0165a46ea37454b5a57255917f9260d4c8

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In Genetics

1. J. Egan
2. Ian B. Dodd
3. D. Court
4. K. Shearwin
5. Rachel A. Schubert

In Molecular Biology

1. J. Egan
2. Ian B. Dodd
3. D. Court
4. K. Shearwin
5. Rachel A. Schubert

Citations in the corpus

• Transcriptional Regulation by the Numbers 1: Models (2004, unknown): “In a companion paper [1], these ideas are applied to several case studies which illustrate the use of the general formalism.”
• Cro’s role in the CI–Cro bistable switch is critical for λ’s transition from lysogeny to lytic development (2007, background): “lacZ ( cro) reporter to CI (LacZ values divided by 5) (Dodd et al. 2004).”
• A New Look at Bacteriophage λ Genetic Networks (2006, background): “These two sets of tetramers interact to form an octamer looping the DNA between OL and OR (Fig. 2) and generating a more stable repression complex of the early promoters (15, 17 , 52, 64).”