Format

Send to

Choose Destination
Int J Hematol. 2008 Sep;88(2):134-138. doi: 10.1007/s12185-008-0121-4. Epub 2008 Jul 2.

Genetic evidence of PEBP2beta-independent activation of Runx1 in the murine embryo.

Author information

1
Institute of Basic Medical Sciences and Center for Tsukuba Advanced Research Alliance, University of Tsukuba, 1-1-1 Tennodai, Tsukuba, Ibaraki, 305-8575, Japan.
2
Institute of Molecular and Cell Biology, 61 Biopolis Drive, Proteos, Singapore, 138673, Singapore.
3
Institute for Virus Research, Kyoto University, Shogoin-Kawaharacho, Kyoto, 606-8507, Japan.
4
Institute of Molecular and Cell Biology, 61 Biopolis Drive, Proteos, Singapore, 138673, Singapore. motomi@imcb.a-star.edu.sg.
5
Oncology Research Institute, National University of Singapore, Singapore, 138673, Singapore. motomi@imcb.a-star.edu.sg.
6
JST-ERATO Environmental Response Project, Tsukuba, Ibaraki, 305-8575, Japan.
7
Oncology Research Institute, National University of Singapore, Singapore, 138673, Singapore.

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, PEBP2beta/CBFbeta, are almost identical in phenotype to Runx1 (-/-) mice, PEBP2beta 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 PEBP2beta-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, PEBP2beta-independent Runx1 activation can occur in vivo. This observation sheds new light on the mechanism(s) that regulate the activity of Runx transcription factors.

PMID:
18594778
DOI:
10.1007/s12185-008-0121-4
[Indexed for MEDLINE]

Supplemental Content

Full text links

Icon for Springer
Loading ...
Support Center