Tissue specific sequence motifs in the enhancer of the leukaemogenic mouse retrovirus SL3-3

The long terminal repeat (LTR) of the retrovirus SL3-3 determines its tropism for T-lymphocytes and its ability to induce T-cell lymphomas in mice. We have studied the ability of different DNA sequences located upstream of the "TATA" box in the LTR of SL3-3 to enhance transcription in T-lymphocyte cell lines and other cell lines, employing a transient assay and quantitative S1 nuclease mapping. The enhancer was found to be composed of many DNA domains which determines different activities in different cell lines. We find enhancer sequence motifs with a high T-lymphocyte specificity in the DNA repetitions of the LTR, and other enhancer motifs active in a broader range of cells in the surrounding DNA segments. The localization of sequences preferentially active in T-cells within the repeated sequences containing differences between SL3-3 and the very closely related Akv virus, which is without the T cell tropism and leukaemogenicity of SL3-3, supports the notion that the enhancer sequence motifs with T-cell preferences are primary determinants of these properties.