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Molecular and Cellular Biology, April 1999, p. 3051-3061, Vol. 19, No. 4
0270-7306/99/$04.00+0
Copyright © 1999, American Society for Microbiology. All rights reserved.

HOXA9 Forms Triple Complexes with PBX2 and MEIS1 in Myeloid Cells

Wei-Fang Shen,1 Sophia Rozenfeld,1 Angela Kwong,2 Laszlo G. Kömüves,2 H. Jeffrey Lawrence,1 and Corey Largman1,2,*

Departments of Medicine1 and Dermatology,2 University of California VA Medical Center, San Francisco, California

Received 8 September 1998/Returned for modification 26 October 1998/Accepted 11 January 1999

Aberrant activation of the HOX, MEIS, and PBX homeodomain protein families is associated with leukemias, and retrovirally driven coexpression of HOXA9 and MEIS1 is sufficient to induce myeloid leukemia in mice. Previous studies have demonstrated that HOX-9 and HOX-10 paralog proteins are unique among HOX homeodomain proteins in their capacity to form in vitro cooperative DNA binding complexes with either the PBX or MEIS protein. Furthermore, PBX and MEIS proteins have been shown to form in vivo heterodimeric DNA binding complexes with each other. We now show that in vitro DNA site selection for MEIS1 in the presence of HOXA9 and PBX yields a consensus PBX-HOXA9 site. MEIS1 enhances in vitro HOXA9-PBX protein complex formation in the absence of DNA and forms a trimeric electrophoretic mobility shift assay (EMSA) complex with these proteins on an oligonucleotide containing a PBX-HOXA9 site. Myeloid cell nuclear extracts produce EMSA complexes which appear to contain HOXA9, PBX2, and MEIS1, while immunoprecipitation of HOXA9 from these extracts results in coprecipitation of PBX2 and MEIS1. In myeloid cells, HOXA9, MEIS1, and PBX2 are all strongly expressed in the nucleus, where a portion of their signals are colocalized within nuclear speckles. However, cotransfection of HOXA9 and PBX2 with or without MEIS1 minimally influences transcription of a reporter gene containing multiple PBX-HOXA9 binding sites. Taken together, these data suggest that in myeloid leukemia cells MEIS1 forms trimeric complexes with PBX and HOXA9, which in turn can bind to consensus PBX-HOXA9 DNA targets.

* Corresponding author. Mailing address: VA Medical Center (151H), 4150 Clement St., San Francisco, CA 94121. Phone: (415) 750-2254. Fax: (415) 221-4262. E-mail: largman{at}cgl.ucsf.edu.

Molecular and Cellular Biology, April 1999, p. 3051-3061, Vol. 19, No. 4
0270-7306/99/$04.00+0
Copyright © 1999, American Society for Microbiology. All rights reserved.


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