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Molecular and Cellular Biology, March 1999, p. 2231-2241, Vol. 19, No. 3
0270-7306/99/$04.00+0
Copyright © 1999, American Society for Microbiology. All rights reserved.

The Highly Conserved beta -Hairpin of the Paired DNA-Binding Domain Is Required for Assembly of Pax-Ets Ternary Complexes

William Wheat,1 Daniel Fitzsimmons,1,2 Heidi Lennox,1 Susan R. Krautkramer,1,3 Lisa N. Gentile,4,dagger Lawrence P. McIntosh,4 and James Hagman1,2,3,*

Division of Basic Immunology, Department of Medicine, National Jewish Medical and Research Center, Denver, Colorado 802061; Department of Immunology2 and Cancer Center,3 University of Colorado Health Sciences Center, Denver, Colorado 80262; and Department of Biochemistry and Molecular Biology, and Department of Chemistry, University of British Columbia, Vancouver, British Columbia V6T 1Z3, Canada4

Received 19 August 1998/Returned for modification 14 October 1998/Accepted 11 November 1998

Pax family transcription factors bind DNA through the paired domain. This domain, which is comprised of two helix-turn-helix motifs and a beta -hairpin structure, is a target of mutations in congenital disorders of mice and humans. Previously, we showed that Pax-5 (B-cell-specific activator protein) recruits proteins of the Ets proto-oncogene family to bind a composite DNA site that is essential for efficient transcription of the early-B-cell-specific mb-1 promoter. Here, evidence is provided for specific interactions between Ets-1 and the amino-terminal subdomains of Pax proteins. By tethering deletion fragments of Pax-5 to a heterologous DNA-binding domain, we show that 73 amino acids (amino acids 12 to 84) of its amino-terminal subdomain can recruit the ETS domain of Ets-1 to bind the composite site. Furthermore, an amino acid (Gln22) within the highly conserved beta -hairpin motif of Pax-5 is essential for efficient recruitment of Ets-1. The ability to recruit Ets proteins to bind DNA is a shared property of Pax proteins, as demonstrated by cooperative DNA binding of Ets-1 with sequences derived from the paired domains of Pax-2 and Pax-3. The strict conservation of sequences required for recruitment of Ets proteins suggests that Pax-Ets interactions are important for regulating transcription in diverse tissues during cellular differentiation.

* Corresponding author. Mailing address: Division of Basic Immunology, National Jewish Medical and Research Center, 1400 Jackson St., K516B, Denver, CO 80206. Phone: (303) 398-1398. Fax: (303) 398-1396. E-mail: hagmanj{at}njc.org.

dagger Present address: Department of Life Sciences, University of New England, Biddeford, ME 04005.

Molecular and Cellular Biology, March 1999, p. 2231-2241, Vol. 19, No. 3
0270-7306/99/$04.00+0
Copyright © 1999, American Society for Microbiology. All rights reserved.


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