title: The Wnt/β-catenin pathway regulates the expression of the miR-302 cluster in mouse ESCs and P19 cells.
abstract: MicroRNAs of the miR-302 cluster are involved in early embryonic development and somatic cell reprogramming. Expression of the miR-302 gene is regulated by the binding of the pluripotency factors Oct4, Sox2 and Nanog to the miR-302 promoter. The specific expression pattern of the miR-302 gene suggested that additional transcription factors might be involved in its regulation. Here, we show that the miR-302 promoter is a direct target of the Wnt/β-catenin signaling pathway. We found that the miR-302 promoter contains three different functional Tcf/Lef binding sites. Two of the three sites were located within the cluster of Oct4/Sox2/Nanog binding sites and were essential for Wnt/β-catenin-mediated regulation of the miR-302 gene. Tcf3, the only Tcf/Lef factor that bound to the miR-302 promoter, acted as a repressor of miR-302 transcription. Interestingly, mutations in the two Tcf/Lef binding sites and the Oct4/Nanog binding sites abolished miR-302 promoter responsiveness to Wnt signaling, suggesting that the Tcf/Lef and the Oct4/Nanog sites interact genetically.
authors.affiliation: Max-Planck Institute of Immunobiology and Epigenetics, Freiburg, Germany ; University of Freiburg Faculty of Biology, Freiburg, Germany.
authors.forename: Christien
authors.initials: C
authors.lastname: Bräutigam
authors.forename: Angelo
authors.initials: A
authors.lastname: Raggioli
authors.forename: Jennifer
authors.initials: J
authors.lastname: Winter
mesh_terms: D000818:Animals; D001665:Binding Sites; D045744:Cell Line, Tumor; D053595:Embryonic Stem Cells / Q000378:metabolism*; D005786:Gene Expression Regulation; D055786:Gene Knockout Techniques; D051379:Mice; D035683:MicroRNAs / Q000235:genetics*; D011401:Promoter Regions, Genetic / Q000235:genetics; D051820:TCF Transcription Factors / Q000378:metabolism; D014158:Transcription, Genetic; D060449:Wnt Signaling Pathway; D051176:beta Catenin / Q000172:deficiency / Q000235:genetics / Q000378:metabolism*
chemical_list: C558265:MIRN302 microRNA, mouse; D035683:MicroRNAs; D051820:TCF Transcription Factors; D051176:beta Catenin
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