Members of the GATA family of transcription factors bind to the U3 region of Cas-Br-E and graffi retroviruses and transactivate their expression.
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.
Barat
C
C
Laboratoire de Biologie Moléculaire, Département de Sciences Biologiques, Université du Québec à Montréal, Montréal, Québec, Canada H3C 3P8.
Rassart
E
E
D000818:Animals; D001483:Base Sequence; D001665:Binding Sites; D002460:Cell Line; D004268:DNA-Binding Proteins / Q000378:metabolism*; D050981:Erythroid-Specific DNA-Binding Factors; D050982:GATA1 Transcription Factor; D050989:GATA2 Transcription Factor; D050990:GATA3 Transcription Factor; D006801:Humans; D009052:Leukemia Virus, Murine / Q000235:genetics*; D051379:Mice; D008969:Molecular Sequence Data; D012091:Repetitive Sequences, Nucleic Acid; D015534:Trans-Activators / Q000378:metabolism*; D014157:Transcription Factors / Q000378:metabolism*; D015533:Transcriptional Activation
D004268:DNA-Binding Proteins; D050981:Erythroid-Specific DNA-Binding Factors; D050982:GATA1 Transcription Factor; C494688:GATA1 protein, human; D050989:GATA2 Transcription Factor; C494711:GATA2 protein, human; D050990:GATA3 Transcription Factor; C494749:GATA3 protein, human; C494689:Gata1 protein, mouse; C494712:Gata2 protein, mouse; C494748:Gata3 protein, mouse; D015534:Trans-Activators; D014157:Transcription Factors