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

Matías A. Medina, Giorgia D. Ugarte, Macarena F. Vargas, Miguel E. Avila, David Necuñir, Alvaro A. Elorza, Soraya E. Gutiérrez, Giancarlo V. De Ferrari

Research output: Contribution to journalArticle

8 Citations (Scopus)

Abstract

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.

Original languageEnglish
Pages (from-to)1460-1467
Number of pages8
JournalJournal of Cellular Physiology
Volume231
Issue number7
DOIs
Publication statusPublished - 1 Jul 2016

ASJC Scopus subject areas

  • Medicine(all)
  • Physiology
  • Clinical Biochemistry
  • Cell Biology

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