Bracken, Cameron PGregory, Philip AKolensnikoff, NatashaBert, Andrew JWang, JunShannon, M FrancesGoodall, Gregory J2015-12-080008-5472http://hdl.handle.net/1885/35221Epithelial to mesenchymal transition occurs during embryologic development to allow tissue remodeling and is proposed to be a key step in the metastasis of epithelial-derived tumors. The miR-200 family of microRNAs plays a major role in specifying the epithelial phenotype by preventing expression of the transcription repressors, ZEB1/δEF1 and SIP1/ZEB2. We show here that miR-200a, miR-200b, and the related miR-429 are all encoded on a 7.5-kb polycistronic primary miRNA (pri-miR) transcript. We show that the promoter for the pri-miR is located within a 300-bp segment located 4 kb upstream of miR-200b. This promoter region is sufficient to confer expression in epithelial cells and is repressed in mesenchymal cells by ZEB1 and SIP1 through their binding to a conserved pair of ZEB-type E-box elements located proximal to the transcription start site. These findings establish a double-negative feedback loop controlling ZEB1-SIP1 and miR-200 family expression that regulates cellular phenotype and has direct relevance to the role of these factors in tumor progression.Keywords: microRNA; microRNA 200a; microRNA 200b; microRNA 429; transcription factor; transcription factor SIP1'; transcription factor ZEB1; unclassified drug; animal cell; article; binding kinetics; cistron; controlled study; E box element; embryo development; epi200810.1158/0008-5472.CAN-08-19422015-12-08