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PLoS One ; 8(9): e75315, 2013.
Artigo em Inglês | MEDLINE | ID: mdl-24040406

RESUMO

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/ß-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/ß-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.


Assuntos
Células-Tronco Embrionárias/metabolismo , Regulação da Expressão Gênica , MicroRNAs/genética , Via de Sinalização Wnt , beta Catenina/metabolismo , Animais , Sítios de Ligação , Linhagem Celular Tumoral , Técnicas de Inativação de Genes , Camundongos , Regiões Promotoras Genéticas/genética , Fatores de Transcrição TCF/metabolismo , Transcrição Gênica , beta Catenina/deficiência , beta Catenina/genética
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