Overexpression of Ets-1 in human hematopoietic progenitor cells blocks erythroid and promotes megakaryocytic differentiation

V. Lulli, P. Romania, O. Morsilli, M. Gabbianelli, A. Pagliuca, S. Mazzeo, U. Testa, C. Peschle, G. Marziali

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Abstract

Ets-1 is a widely expressed transcription factor implicated in development, tumorigenesis and hematopoiesis. We analyzed Ets-1 gene expression during human erythroid and megakaryocytic (MK) differentiation in unilineage cultures of CD34+ progenitor cells. During erythroid maturation, Ets-1 is downmodulated and exported from the nucleus into the cytoplasm through an active mechanism mediated by a leucine-rich nuclear export signal. In contrast, during megakaryocytopoiesis Ets-1 increases and remains localized in the nucleus up to terminal maturation. Overexpression of Ets-1 in erythroid cells blocks maturation at the polychromatophilic stage, increases GATA-2 and decreases both GATA-1 and erythropoietin receptor expression. Conversely, Ets-1 overexpressing megakaryocytes are characterized by enhanced differentiation and maturation, coupled with upmodulation of GATA-2 and megakaryocyte-specific genes. We show that Ets-1 binds to and activates the GATA-2 promoter, in vitro and in vivo, indicating that one of the pathways through which Ets-1 blocks erythroid and promotes MK differentiation is via upmodulation of GATA-2 expression.

Original languageEnglish
Pages (from-to)1064-1074
Number of pages11
JournalCell Death and Differentiation
Volume13
Issue number7
DOIs
Publication statusPublished - Jul 2006

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Keywords

  • Ets binding sites
  • GATA-2
  • Nuclear export signal
  • Subcellular localization
  • Transcription factors

ASJC Scopus subject areas

  • Cell Biology

Cite this

Lulli, V., Romania, P., Morsilli, O., Gabbianelli, M., Pagliuca, A., Mazzeo, S., Testa, U., Peschle, C., & Marziali, G. (2006). Overexpression of Ets-1 in human hematopoietic progenitor cells blocks erythroid and promotes megakaryocytic differentiation. Cell Death and Differentiation, 13(7), 1064-1074. https://doi.org/10.1038/sj.cdd.4401811