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Prepublished online as a Blood First Edition Paper on June 5, 2003; DOI 10.1182/blood-2003-01-0251.
Submitted January 29, 2003
Accepted May 26, 2003
NF-Y cooperates with USF1/2 to induce the hematopoietic expression of HOXB4
Jiang Zhu, Diane M Giannola, Yi Zhang, Adam J Rivera, and Stephen G Emerson*
Departments of Medicine and Pediatrics, University of Pennsylvania, Philadelphia, PA, USA
* Corresponding author; email: emersons{at}mail.med.upenn.edu.
The transcription factor HOXB4 is preferentially expressed in immature hematopoietic cells and implicated in the transition from primitive hematopoiesis to definitive hematopoiesis as well as in immature hematopoietic cell proliferation and differentiation. We previously identified HxRE-1 and HxRE-2/E-box as two critical DNA binding sites of HOXB4 promoter active in hematopoietic cells and demonstrated that USF1/2 activates HOXB4 transcription through its binding to E-box site. Here we report that the trimeric regulatory complex NF-Y is the factor that recognizes HxRE-1 and activates the HOXB4 promoter in hematopoietic cells. We further show that NF-Y interacts biochemically with USF1/2 on the HOXB4 promoter, and that the formation of this NF-Y/USF1/2 complex is required for the full activity of the HOXB4 promoter. Most importantly, NF-Ya subunit protein levels are found to be lower in c-Kit-Gr-1+ granulocytic BM cells than in c-Kit+ immature BM cells, in parallel with a reduction of NF-Y occupancy on the HOXB4 promoter as shown by ChIP assay. These results suggest that NF-Y is a developmentally regulated inducer of the HOXB4 gene in hematopoietic cells.
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