Alternative RUNX1 Promoter Regulation by Wnt/β-Catenin Signaling in Leukemia Cells and Human Hematopoietic Progenitors.

Autor: Medina MA; Faculty of Biological Sciences and Faculty of Medicine, Center for Biomedical Research, Universidad Andres Bello, Santiago, Chile., Ugarte GD; Faculty of Biological Sciences and Faculty of Medicine, Center for Biomedical Research, Universidad Andres Bello, Santiago, Chile., Vargas MF; Faculty of Biological Sciences and Faculty of Medicine, Center for Biomedical Research, Universidad Andres Bello, Santiago, Chile., Avila ME; Faculty of Biological Sciences and Faculty of Medicine, Center for Biomedical Research, Universidad Andres Bello, Santiago, Chile., Necuñir D; Faculty of Biological Sciences and Faculty of Medicine, Center for Biomedical Research, Universidad Andres Bello, Santiago, Chile., Elorza AA; Faculty of Biological Sciences and Faculty of Medicine, Center for Biomedical Research, Universidad Andres Bello, Santiago, Chile.; Millennium Institute on Immunology and Immunotherapy, Santiago, Chile., Gutiérrez SE; Department of Biochemistry and Molecular Biology, Faculty of Biological Sciences, Universidad de Concepción, Concepción, Chile., De Ferrari GV; Faculty of Biological Sciences and Faculty of Medicine, Center for Biomedical Research, Universidad Andres Bello, Santiago, Chile.
Jazyk: angličtina
Zdroj: Journal of cellular physiology [J Cell Physiol] 2016 Jul; Vol. 231 (7), pp. 1460-7. Date of Electronic Publication: 2016 Feb 11.
DOI: 10.1002/jcp.25258
Abstrakt: 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/-16 bp 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.)
Databáze: MEDLINE
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