N. Kraut et al., A FUNCTIONAL ETS DNA-BINDING DOMAIN IS REQUIRED TO MAINTAIN MULTIPOTENCY OF HEMATOPOIETIC PROGENITORS TRANSFORMED BY MYB-ETS, Genes & development, 8(1), 1994, pp. 33-44
Earlier work demonstrated that the Myb-Ets fusion protein of E26 avian
leukemia virus induces the proliferation of multipotent hematopoietic
progenitors (MEPs). These progenitors differentiate spontaneously at
low frequencies along the erythroid lineage, and following the introdu
ction of kinase/ras-type oncogenes or treatment with TPA, they are ind
uced to differentiate along the myelomonocytic and eosinophilic lineag
es. Here, we show that the ts1.1 mutant of E26 encodes an Ets DNA-bind
ing domain that is both defective and thermolabile for binding of spec
ific DNA sequences. Correlating with this, ts1.1 MEP colonies transfor
med at the permissive temperature exhibit elevated levels of erythroid
cells and eosinophils, whereas at the nonpermissive temperature they
are induced to differentiate along the erythroid and myelomonocytic li
neages and, to a lesser extent, along the eosinophil lineage. Inductio
n of the former two lineages cannot be separated by pulse shift experi
ments and is essentially completed 2.5 days after temperature shift. O
ur results indicate that the Ets portion of the Myb-Ets fusion protein
inhibits the lineage commitment of multipotent hematopoietic progenit
ors, probably via binding to regulatory DNA sequences of specific targ
et genes.