Phylogenesis and regulated expression of the RUNT domain transcription factors RUNX1 and RUNX3.
The RUNX transcription factors are key regulators of lineage specific gene expression in developmental pathways. The mammalian RUNX genes arose early in evolution and maintained extensive structural similarities. Sequence analysis suggested that RUNX3 is the most ancient of the three mammalian genes, consistent with its role in neurogenesis of the monosynaptic reflex arc, the simplest neuronal response circuit, found in Cnidarians, the most primitive animals. All RUNX proteins bind to the same DNA motif and act as activators or repressors of transcription through recruitment of common transcriptional modulators. Nevertheless, analysis of Runx1 and Runx3 expression during embryogenesis revealed that their function is not redundant. In adults both Runx1 and Runx3 are highly expressed in the hematopoietic system. At early embryonic stages we found strong Runx3 expression in dorsal root ganglia neurons, confined to TrkC sensory neurons. In the absence of Runx3, knockout mice develop severe ataxia due to the early death of the TrkC neurons. Other phenotypic defects of Runx3 KO mice including abnormalities in thymopoiesis are also being investigated.
Department of Molecular Genetics, Weizmann Institute of Science, Rehovot 76100, Israel.
Ditsa
D
Levanon
Gustavo
G
Glusman
David
D
Bettoun
Edna
E
Ben-Asher
Varda
V
Negreanu
Yael
Y
Bernstein
Catherine
C
Harris-Cerruti
Ori
O
Brenner
Raya
R
Eilam
Joseph
J
Lotem
Ofer
O
Fainaru
Dalia
D
Goldenberg
Amir
A
Pozner
Eilon
E
Woolf
Cuiying
C
Xiao
Merav
M
Yarmus
Yoram
Y
Groner
D000818:Animals; D050677:Core Binding Factor Alpha 3 Subunit; D004268:DNA-Binding Proteins / Q000145:classification / Q000235:genetics*; D029721:Drosophila Proteins; D005786:Gene Expression Regulation; D006801:Humans; D008322:Mammals; D009687:Nuclear Proteins; D010802:Phylogeny; D014157:Transcription Factors / Q000145:classification / Q000235:genetics*
D050677:Core Binding Factor Alpha 3 Subunit; D004268:DNA-Binding Proteins; D029721:Drosophila Proteins; D009687:Nuclear Proteins; C493729:Runx3 protein, human; D014157:Transcription Factors; C080833:run protein, Drosophila