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 journalArticlepeer-review

    142 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 - Jun 1 2005

    All Science Journal Classification (ASJC) codes

    • Neuroscience(all)
    • Molecular Biology
    • Biochemistry, Genetics and Molecular Biology(all)
    • Immunology and Microbiology(all)

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