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

doi:10.1038/sj.emboj.7600679

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 journal › Article › peer-review

164 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 language	English
Pages (from-to)	1976-1987
Number of pages	12
Journal	EMBO Journal
Volume	24
Issue number	11
DOIs	https://doi.org/10.1038/sj.emboj.7600679
Publication status	Published - 2005 Jun 1
Externally published	Yes

Keywords

Angiopoiesis
Evi1
GATA-2
Hematopoiesis

ASJC Scopus subject areas

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

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title = "Oncogenic transcription factor Evi1 regulates hematopoietic stem cell proliferation through GATA-2 expression",

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.",

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author = "Hiromi Yuasa and Yuichi Oike and Atsushi Iwama and Ichiro Nishikata and Daisuke Sugiyama and Archibald Perkins and Mucenski, {Michael L.} and Toshio Suda and Kazuhiro Morishita",

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T1 - Oncogenic transcription factor Evi1 regulates hematopoietic stem cell proliferation through GATA-2 expression

AU - Yuasa, Hiromi

AU - Oike, Yuichi

AU - Iwama, Atsushi

AU - Nishikata, Ichiro

AU - Sugiyama, Daisuke

AU - Perkins, Archibald

AU - Mucenski, Michael L.

AU - Suda, Toshio

AU - Morishita, Kazuhiro

PY - 2005/6/1

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N2 - 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.

AB - 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.

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KW - Evi1

KW - GATA-2

KW - Hematopoiesis

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

Abstract

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