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

研究成果: Article査読

150 被引用数 (Scopus)

抄録

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.

本文言語English
ページ(範囲)1976-1987
ページ数12
ジャーナルEMBO Journal
24
11
DOI
出版ステータスPublished - 2005 6 1

ASJC Scopus subject areas

  • 神経科学(全般)
  • 分子生物学
  • 生化学、遺伝学、分子生物学(全般)
  • 免疫学および微生物学(全般)

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