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Type: Journal article
Title: Enhancer-like long-range transcriptional activation by λ CI-mediated DNA looping
Other Titles: Enhancer-like long-range transcriptional activation by lambda CI-mediated DNA looping
Author: Cui, L.
Murchland, I.
Shearwin, K.
Dodd, I.
Citation: Proceedings of the National Academy of Sciences of USA, 2013; 110(8):2922-2927
Publisher: National Academy of Sciences
Issue Date: 2013
ISSN: 1091-6490
Statement of
Lun Cui, Iain Murchland, Keith E. Shearwin, and Ian B. Dodd
Abstract: How distant enhancer elements regulate the assembly of a transcription complex at a promoter remains poorly understood. Here, we use long-range gene regulation by the bacteriophage λ CI protein as a powerful system to examine this process in vivo. A 2.3-kb DNA loop, formed by CI bridging its binding sites at OR and OL, is known already to enhance repression at the lysogenic promoter PRM, located at OR. Here, we show that CI looping also activates PRM by allowing the C-terminal domain of the α subunit of the RNA polymerase bound at PRM to contact a DNA site adjacent to the distal CI sites at OL. Our results establish OL as a multifaceted enhancer element, able to activate transcription from long distances independently of orientation and position. We develop a physicochemical model of our in vivo data and use it to show that the observed activation is consistent with a simple recruitment mechanism, where the α–C-terminal domain to DNA contact need only provide ∼2.7 kcal/mol of additional binding energy for RNA polymerase. Structural modeling of this complete enhancer–promoter complex reveals how the contact is achieved and regulated, and suggests that distal enhancer elements, once appropriately positioned at the promoter, can function in essentially the same way as proximal promoter elements.
Keywords: Bacteriophage lambda; DNA, Viral; Models, Molecular; Enhancer Elements, Genetic; Transcriptional Activation
Rights: © Authors
RMID: 0020125834
DOI: 10.1073/pnas.1221322110
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Appears in Collections:Molecular and Biomedical Science publications

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