Genetic evidence of PEBP2beta-independent activation of Runx1 in the murine embryo.
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.
Yokomizo
Tomomasa
T
Institute of Basic Medical Sciences and Center for Tsukuba Advanced Research Alliance, University of Tsukuba, 1-1-1 Tennodai, Tsukuba, Ibaraki, 305-8575, Japan.
Yanagida
Masatoshi
M
Institute of Molecular and Cell Biology, 61 Biopolis Drive, Proteos, Singapore, 138673, Singapore.
Huang
Gang
G
Institute for Virus Research, Kyoto University, Shogoin-Kawaharacho, Kyoto, 606-8507, Japan.
Osato
Motomi
M
Institute of Molecular and Cell Biology, 61 Biopolis Drive, Proteos, Singapore, 138673, Singapore. motomi@imcb.a-star.edu.sg.|Oncology Research Institute, National University of Singapore, Singapore, 138673, Singapore. motomi@imcb.a-star.edu.sg.
Honda
Chikako
C
Institute of Basic Medical Sciences and Center for Tsukuba Advanced Research Alliance, University of Tsukuba, 1-1-1 Tennodai, Tsukuba, Ibaraki, 305-8575, Japan.
Ema
Masatsugu
M
Institute of Basic Medical Sciences and Center for Tsukuba Advanced Research Alliance, University of Tsukuba, 1-1-1 Tennodai, Tsukuba, Ibaraki, 305-8575, Japan.
Takahashi
Satoru
S
Institute of Basic Medical Sciences and Center for Tsukuba Advanced Research Alliance, University of Tsukuba, 1-1-1 Tennodai, Tsukuba, Ibaraki, 305-8575, Japan.
Yamamoto
Masayuki
M
Institute of Basic Medical Sciences and Center for Tsukuba Advanced Research Alliance, University of Tsukuba, 1-1-1 Tennodai, Tsukuba, Ibaraki, 305-8575, Japan.|JST-ERATO Environmental Response Project, Tsukuba, Ibaraki, 305-8575, Japan.
Ito
Yoshiaki
Y
Institute of Molecular and Cell Biology, 61 Biopolis Drive, Proteos, Singapore, 138673, Singapore.|Oncology Research Institute, National University of Singapore, Singapore, 138673, Singapore.
D000818:Animals; D002543:Cerebral Hemorrhage / Q000235:genetics* / Q000378:metabolism / Q000503:physiopathology; D050676:Core Binding Factor Alpha 2 Subunit / Q000235:genetics* / Q000378:metabolism*; D050658:Core Binding Factor beta Subunit / Q000235:genetics* / Q000378:metabolism*; D050982:GATA1 Transcription Factor / Q000235:genetics / Q000378:metabolism; D018507:Gene Expression Regulation, Developmental; D005804:Genes, Lethal; D005838:Genotype; D006410:Hematopoiesis / Q000235:genetics; D051379:Mice; D008822:Mice, Transgenic; D010641:Phenotype
D050676:Core Binding Factor Alpha 2 Subunit; D050658:Core Binding Factor beta Subunit; D050982:GATA1 Transcription Factor; C494689:Gata1 protein, mouse; C493726:Runx1 protein, mouse