Alternative Runx1 Promoter Regulation By Wnt/Beta-Catenin Signaling In Leukemia Cells And Human Hematopoietic Progenitors

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 -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/-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 -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/-catenin signaling that may be important in normal hematopoiesis or its transition into malignant stem cells during the onset or progression of leukemia. J. Cell. Physiol. 231: 1460-1467, 2016. (c) 2015 Wiley Periodicals, Inc.