{"doi":"10.1073/pnas.0902454106","title":"Transcription factors mediate long-range enhancer–promoter interactions","abstract":"<jats:p>We examined how remote enhancers establish physical communication with target promoters to activate gene transcription in response to environmental signals. Although the natural IFN-β 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-β 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 λ repressor, which is capable of loop formation, rescues enhancer function from a distance by re-establishing enhancer–promoter loop formation.</jats:p>","journal":"Proceedings of the National Academy of Sciences","year":2009,"id":15994,"datarank":6.396560767089737,"base_score":5.308267697401205,"endowment":5.308267697401205,"self_citation_contribution":0.7962401546101808,"citation_network_contribution":5.600320612479556,"self_endowment_contribution":0.7962401546101808,"citer_contribution":5.600320612479556,"corpus_percentile":null,"corpus_rank":null,"citation_count":201,"citer_count":188,"citers_with_citation_signal":162,"citers_with_endowment":162,"datacite_reuse_total":25,"is_dataset":false,"is_dataset_confidence":null,"is_oa":false,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":119760,"name":"Daniel J. 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and Chromatin Dynamics","RNA and protein synthesis mechanisms","RNA Research and Splicing","Biology","Medicine","Chromatin Immunoprecipitation","DNA","DNA Primers","Enhancer Elements, Genetic","Gene Expression Regulation","HeLa Cells","Humans","Interferon-beta","Polymerase Chain Reaction","Promoter Regions, Genetic","Transcription Factors","Transcription, Genetic"],"mesh_terms":["DNA","Enhancer Elements, Genetic","Gene Expression Regulation","HeLa Cells","Humans","Promoter Regions, Genetic","Transcription Factors","Transcription, Genetic","Polymerase Chain Reaction","Interferon-beta","DNA Primers","Chromatin Immunoprecipitation","Hela Cells"],"keywords":["Enhancer","Promoter","Enhancer RNAs","Biology","Transcription factor","Transcription (linguistics)","Response element","Enhancer trap","Upstream activating sequence","Chromatin","Repressor","Genetics","Gene","Molecular biology","Gene expression"],"sdg_mappings":[{"sdg_number":0,"sdg_label":"Life in 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