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Medina M.A.,Center for Biomedical ResearchUniversidad Andres BelloSantiagoChile | Ugarte G.D.,Center for Biomedical ResearchUniversidad Andres BelloSantiagoChile | Vargas M.F.,Center for Biomedical ResearchUniversidad Andres BelloSantiagoChile | Avila M.E.,Center for Biomedical ResearchUniversidad Andres BelloSantiagoChile | And 3 more authors.
Journal of Cellular Physiology | Year: 2016

Two distantly located promoter regions regulate the dynamic expression of RUNX genes during development: distal P1 and proximal P2 promoters. We have recently described that β-catenin increases total Runx1 mRNA levels in human CD34+ hematopoietic progenitors and enhances spatial proximity with its translocation partner ETO. Here, we report that induction of Wnt/β-catenin signaling in HL60 and Jurkat leukemia-derived cell lines and CD34+ progenitors selectively activate the production of the longer distal P1-Runx1 mRNA isoform. Gain- and loss-of-function experiments revealed that the differential increase in P1-Runx1 expression is accomplished through a minimal β-catenin responsive region that includes a highly conserved TCF/LEF-binding element, located -20/-16bp upstream of the canonical distal P1-Runx1 transcription start site. We conclude that the distal P1-Runx1 promoter is a direct transcriptional target of Wnt/β-catenin signaling that may be important in normal hematopoiesis or its transition into malignant stem cells during the onset or progression of leukemia. © 2015 Wiley Periodicals, Inc. Source

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