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

Resultado de la investigación: Article

8 Citas (Scopus)

Resumen

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.

Idioma originalEnglish
Páginas (desde-hasta)1460-1467
Número de páginas8
PublicaciónJournal of Cellular Physiology
Volumen231
N.º7
DOI
EstadoPublished - 1 jul 2016

Huella dactilar

Catenins
Hematopoietic Stem Cells
Leukemia
RNA Isoforms
Transcription Initiation Site
Hematopoiesis
Stem cells
Genetic Promoter Regions
Stem Cells
Genes
Cells
Gene Expression
Cell Line
Messenger RNA
Experiments

ASJC Scopus subject areas

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

Citar esto

Medina, Matías A. ; Ugarte, Giorgia D. ; Vargas, Macarena F. ; Avila, Miguel E. ; Necuñir, David ; Elorza, Alvaro A. ; Gutiérrez, Soraya E. ; De Ferrari, Giancarlo V. / Alternative RUNX1 Promoter Regulation by Wnt/β-Catenin Signaling in Leukemia Cells and Human Hematopoietic Progenitors. En: Journal of Cellular Physiology. 2016 ; Vol. 231, N.º 7. pp. 1460-1467.
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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.",
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Alternative RUNX1 Promoter Regulation by Wnt/β-Catenin Signaling in Leukemia Cells and Human Hematopoietic Progenitors. / Medina, Matías A.; Ugarte, Giorgia D.; Vargas, Macarena F.; Avila, Miguel E.; Necuñir, David; Elorza, Alvaro A.; Gutiérrez, Soraya E.; De Ferrari, Giancarlo V.

En: Journal of Cellular Physiology, Vol. 231, N.º 7, 01.07.2016, p. 1460-1467.

Resultado de la investigación: Article

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AU - Medina, Matías A.

AU - Ugarte, Giorgia D.

AU - Vargas, Macarena F.

AU - Avila, Miguel E.

AU - Necuñir, David

AU - Elorza, Alvaro A.

AU - Gutiérrez, Soraya E.

AU - De Ferrari, Giancarlo V.

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AB - 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.

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