Genetic evidence of PEBP2β-independent activation of Runx1 in the murine embryo

Tomomasa Yokomizo, Masatoshi Yanagida, Gang Huang, Motomi Osato, Chikako Honda, Masatsugu Ema, Satoru Takahashi, Masayuki Yamamoto, Yoshiaki Ito

Research output: Contribution to journalArticlepeer-review

3 Citations (Scopus)

Abstract

The Runx1/AML1 transcription factor is required for the generation of hematopoietic stem cells and is one of the most frequently targeted genes in human leukemia. Runx1-deficient mice die around embryonic day (E)12.5 due to severe hemorrhage in the central nervous system and the complete absence of definitive hematopoietic cells. Since mice lacking the heterodimeric partner of Runx1, PEBP2β/CBFβ, are almost identical in phenotype to Runx1 -/- mice, PEBP2β was believed to be essential for the in vivo function of Runx1. Here we show that transgenic overexpression of Runx1 partially rescues the lethal phenotype of PEBP2β-deficient mice at E12.5. Some of the rescued mice escaped from the severe hemorrhage at E11.5-12.5, although definitive hematopoiesis was not restored. Thus, PEBP2β- independent Runx1 activation can occur in vivo. This observation sheds new light on the mechanism(s) that regulate the activity of Runx transcription factors.

Original languageEnglish
Pages (from-to)134-138
Number of pages5
JournalInternational journal of hematology
Volume88
Issue number2
DOIs
Publication statusPublished - 2008 Sep
Externally publishedYes

Keywords

  • CBF
  • GATA-1
  • Hemangioblast
  • Hematopoietic stem cell
  • PEBP2
  • Runx
  • Vasculogenesis

ASJC Scopus subject areas

  • Hematology

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