Nuclear factors that bind to the U3 region of two murine myeloid leukemia-inducing retroviruses, Cas-Br-E and Graffi

Abstract

Cas-Br-E and Graffi are two myeloid leukemia-inducing murine viruses. Cas-Br-E induces, in NIH-Swiss mice, mostly non-T, non-B leukemia composed of very immature cells with no specific characteristics (Bergeron et al. (1993). Leukemia 7, 954-962). The Graffi murine leukemia virus causes exclusively myeloid leukemia, but the tumor cells are clearly of granulocytic nature (Ru et al. (1993). J. Virol. 67, 4722). We were interested to understand the role of the long terminal repeat (LTR) U3 region in the myeloid specificity of these two retroviruses. We used DNase I footprinting and gel mobility shift assays to identify a number of protein binding sites within Cas-Br-E and Graffi U3 regions. The pattern of protected regions is highly similar for the two viruses. Some factors identified in other murine leukemia viruses, like the core binding factor, also bind to Cas-Br-E and Graffi LTR; however, other binding sites seem specific for these two viruses. Only one difference between them was noted, at the 5' end of the U3 region. Transcriptional activity of both LTRs was also analyzed in various cell lines and compared with other murine leukemia viruses. The results show a slight myeloid specificity for the two LTRs, and indicate that the Graffi enhancer is quite strong in a broad range of cell types.