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

Cas-Br-E and Graffi are two myeloid leukemia-inducing murine viruses. Cas-B r-E induces, in NIH-swiss mice, mostly non-T, non-B leukemia composed of ve ry immature cells with no specific characteristics (Bergeron et ai. (1993). Leukemia 7, 954-962). The Graffi murine leukemia virus causes exclusively myeloid leukemia, but the tumor cells are clearly of granulocytic nature (R u et al. (1993). J. Virol. 67, 4722). We were interested to understand the role of the long terminal repeat (LTR) us region in the myeloid specificity of these two retroviruses. We used DNase I footprinting and gel mobility s hift assays to identify a number of protein binding sites within Cas-Br-E a nd Graffi U3 regions. The pattern of protected regions is highly similar fo r 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; howev er, other binding sites seem specific for these two viruses. Only one diffe rence between them was noted, at the 5' end of the U3 region. Transcription al activity of both LTRs was also analyzed in various cell lines and compar ed with other murine leukemia viruses. The results show a slight myeloid sp ecificity for the two LTRs, and indicate that the Graffi enhancer is guile strong in a broad range of cell types. (C) 1998 Academic Press.