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

Abstract

The ecotropic viral integration site-1 (Evi1) is an oncogenic 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.

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@article{Yuasa2005OncogenicTF, title={Oncogenic transcription factor Evi1 regulates hematopoietic stem cell proliferation through GATA-2 expression.}, author={Hiromi Yuasa and Yuichi Oike and Atsushi Iwama and Ichiro Nishikata and Daisuke Sugiyama and A. S. Perkins and Michael L. Mucenski and Toshio Suda and Kazuhiro Morishita}, journal={The EMBO journal}, year={2005}, volume={24 11}, pages={1976-87} }