The Wnt-β-Catenin Pathway Regulates the Expression of the miR-302 Cluster in Mouse ESCs and P19 CellsReportar como inadecuado




The Wnt-β-Catenin Pathway Regulates the Expression of the miR-302 Cluster in Mouse ESCs and P19 Cells - Descarga este documento en PDF. Documentación en PDF para descargar gratis. Disponible también para leer online.

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.



Autor: Christien Bräutigam, Angelo Raggioli, Jennifer Winter

Fuente: http://plos.srce.hr/



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