Transcription factors mediate long-range enhancer-promoter interactions.


We examined how remote enhancers establish physical communication with target promoters to activate gene transcription in response to environmental signals. Although the natural IFN-beta enhancer is located immediately upstream of the core promoter, it also can function as a classical enhancer element conferring virus infection-dependent activation of heterologous promoters, even when it is placed several kilobases away from these promoters. We demonstrated that the remote IFN-beta enhancer "loops out" the intervening DNA to reach the target promoter. These chromatin loops depend on sequence-specific transcription factors bound to the enhancer and the promoter and thus can explain the specificity observed in enhancer-promoter interactions, especially in complex genetic loci. Transcription factor binding sites scattered between an enhancer and a promoter can work as decoys trapping the enhancer in nonproductive loops, thus resembling insulator elements. Finally, replacement of the transcription factor binding sites involved in DNA looping with those of a heterologous prokaryotic protein, the lambda repressor, which is capable of loop formation, rescues enhancer function from a distance by re-establishing enhancer-promoter loop formation.

DOI: 10.1073/pnas.0902454106

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@article{Nolis2009TranscriptionFM, title={Transcription factors mediate long-range enhancer-promoter interactions.}, author={Ilias K Nolis and Daniel J. J. McKay and Eva Mantouvalou and Stavros Lomvardas and Menie Merika and Dimitris Thanos}, journal={Proceedings of the National Academy of Sciences of the United States of America}, year={2009}, volume={106 48}, pages={20222-7} }