HOX11 is a homeodomain-containing oncogenic transcription factor that immor
talizes hematopoietic precursor cells. The mechanism by which HOX11 facilit
ates this initial step of leukemogenesis is, however, not well understood.
We have used a DNA binding site selection assay to investigate cooperative
DNA binding by HOX11 with other transcription factors. A consensus sequence
was derived and identified as the binding site for the CCAAT-box-binding t
ranscription factors (CTF), HOX11 was shown to interact in vitro and in viv
o with CTF1. Retrovirus-mediated transduction of an antisense CTF1 cDNA dra
matically reduced the proliferative capacity of HOX11-immortalized hematopo
ietic precursor cells. CTF1 is, therefore, the first HOX11 protein partner
identified that plays an important role in hematopoietic precursor cell imm
ortalization.