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J Virol, July 1998, p. 5579-5588, Vol. 72, No. 7
0022-538X/98/$04.00+0
Copyright © 1998, American Society for Microbiology. All rights reserved.

Members of the GATA Family of Transcription Factors Bind to the U3 Region of Cas-Br-E and Graffi Retroviruses and Transactivate Their Expression

Corinne Barat and Eric Rassart*

Laboratoire de Biologie Moléculaire, Département de Sciences Biologiques, Université du Québec à Montréal, Montréal, Québec, Canada H3C 3P8

Received 17 October 1997/Accepted 25 March 1998

Cas-Br-E and Graffi are two murine viruses that induce myeloid leukemia in mice: while Cas-Br-E induces mostly non-T, non-B leukemia composed of very immature cells, Graffi causes exclusively a granulocytic leukemia (E. Rassart, J. Houde, C. Denicourt, M. Ru, C. Barat, E. Edouard, L. Poliquin, and D. Bergeron, Curr. Top. Microbiol. Immunol. 211:201-210, 1995). In an attempt to understand the basis of the myeloid specificity of these two retroviruses, we used DNase I footprinting analysis and gel mobility shift assays to identify a number of protein binding sites within the Cas-Br-E and Graffi U3 regions. Two protected regions include potential GATA binding sites. Methylation interference analysis with different hematopoietic nuclear extracts showed the importance of the G residues in these GATA sites, and supershift assays clearly identified the binding factors as GATA-1, GATA-2, and GATA-3. Transient assays with long terminal repeat (LTR)-chloramphenicol acetyltransferase constructs showed that these three GATA family members are indeed able to transactivate Cas-Br-E and Graffi LTRs. Thus, the availability and relative abundance of the various members of the GATA family of transcription factors in a given cell type could influence the transcriptional tissue specificity of murine leukemia viruses and hence their disease specificity.

* Corresponding author. Mailing address: Laboratoire de biologie moléculaire, Département des Sciences Biologiques, Université du Québec à Montréal, C.P. 8888, Succursale Centre-Ville, Montréal, Québec, Canada H3C 3P8. Phone: (514) 987-3000, ext. 3953. Fax: (514) 987-4647. E-mail: rassart.eric{at}UQAM.ca.

J Virol, July 1998, p. 5579-5588, Vol. 72, No. 7
0022-538X/98/$04.00+0
Copyright © 1998, American Society for Microbiology. All rights reserved.


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