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Enhancers physically interact with transcriptional promoters, looping over distances that can span multiple regulatory elements. Given that enhancer-promoter (EP) interactions generally occur via common protein complexes, it is unclear whether EP pairing is predominantly deterministic or proximity guided. Here, we present cross-organismic evidence suggesting that most EP pairs are compatible, largely determined by physical proximity rather than specific interactions. By reanalyzingdoi:10.1534/g3.116.036228 pmid:27799341 pmcid:PMC5144984 fatcat:rqbw5yjef5dvbocas3n6ndiuaa