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 |
| 巻 | 24 |
| 号 | 11 |
| DOI | |
| 出版ステータス | Published - 2005 6月 1 |
| 外部発表 | はい |
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）