Oncogenic transcription factor Evi1 regulates hematopoietic stem cell proliferation through GATA-2 expression

Hiromi Yuasa, Yuichi Oike, Atsushi Iwama, Ichiro Nishikata, Daisuke Sugiyama, Archibald Perkins, Michael L. Mucenski, Toshio Suda, Kazuhiro Morishita

Research output: Contribution to journalArticle

138 Citations (Scopus)

Abstract

The ecotropic viral integration site-1 (Evi1) is an onco-genic transcription factor in murine and human myeloid leukemia. We herein show that Evi1 is predominantly expressed in hematopoietic stem cells (HSCs) in embryos and adult bone marrows, suggesting a physiological role of Evi1 in HSCs. We therefore investigate the role and authentic target genes of Evi1 in hematopoiesis using Evi1-/- mice, which die at embryonic day 10.5. HSCs in Evi1-/- embryos are markedly decreased in numbers in vivo with defective self-renewing proliferation and repopulating capacity. Notably, expression rate of GATA-2 mRNA, which is essential for proliferation of definitive HSCs, is profoundly reduced in HSCs of Evi1-/- embryos. Restoration of the Evi1 or GATA-2 expression in Evi1-/- HSCs could prevent the failure of in vitro maintenance and proliferation of HSC through upregulation of GATA-2 expression. An analysis of the GATA-2 promoter region revealed that Evi1 directly binds to GATA-2 promoter as an enhancer. Our results reveal that GATA-2 is presumably one of critical targets for Evi1 and that transcription factors regulate the HSC pool hierarchically.

Original languageEnglish
Pages (from-to)1976-1987
Number of pages12
JournalEMBO Journal
Volume24
Issue number11
DOIs
Publication statusPublished - 2005 Jun 1

Fingerprint

Virus Integration
Cell proliferation
Hematopoietic Stem Cells
Stem cells
Transcription Factors
Cell Proliferation
Embryonic Structures
Myeloid Leukemia
Hematopoiesis
Genetic Promoter Regions
Restoration
Bone
Up-Regulation
Genes

Keywords

  • Angiopoiesis
  • Evi1
  • GATA-2
  • Hematopoiesis

ASJC Scopus subject areas

  • Genetics
  • Cell Biology

Cite this

Yuasa, H., Oike, Y., Iwama, A., Nishikata, I., Sugiyama, D., Perkins, A., ... Morishita, K. (2005). Oncogenic transcription factor Evi1 regulates hematopoietic stem cell proliferation through GATA-2 expression. EMBO Journal, 24(11), 1976-1987. https://doi.org/10.1038/sj.emboj.7600679

Oncogenic transcription factor Evi1 regulates hematopoietic stem cell proliferation through GATA-2 expression. / Yuasa, Hiromi; Oike, Yuichi; Iwama, Atsushi; Nishikata, Ichiro; Sugiyama, Daisuke; Perkins, Archibald; Mucenski, Michael L.; Suda, Toshio; Morishita, Kazuhiro.

In: EMBO Journal, Vol. 24, No. 11, 01.06.2005, p. 1976-1987.

Research output: Contribution to journalArticle

Yuasa, H, Oike, Y, Iwama, A, Nishikata, I, Sugiyama, D, Perkins, A, Mucenski, ML, Suda, T & Morishita, K 2005, 'Oncogenic transcription factor Evi1 regulates hematopoietic stem cell proliferation through GATA-2 expression', EMBO Journal, vol. 24, no. 11, pp. 1976-1987. https://doi.org/10.1038/sj.emboj.7600679
Yuasa, Hiromi ; Oike, Yuichi ; Iwama, Atsushi ; Nishikata, Ichiro ; Sugiyama, Daisuke ; Perkins, Archibald ; Mucenski, Michael L. ; Suda, Toshio ; Morishita, Kazuhiro. / Oncogenic transcription factor Evi1 regulates hematopoietic stem cell proliferation through GATA-2 expression. In: EMBO Journal. 2005 ; Vol. 24, No. 11. pp. 1976-1987.
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