The mouse mammary tumor virus env gene contains a transcriptional activator (META) that can control transcription of the adjacent long terminal repeat region. Transcriptional control by META parallels that of several lymphokine genes, being specific to T cells, dependent on their activation, and inhibited by the immunosuppressive drug cyclosporine (CsA). DNase I footprinting indicated that nuclear factors from activated T lymphocytes bound a promoter-proximal site, META(P), and a

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... site, META(D؉), within the 400-base pair META region. Nuclear factors from unstimulated, but not from activated cells, bound a site, META(D؊), adjacent to META(D؉). META(D؉) directed transcription of a linked luciferase gene, and gel shift analysis revealed binding of inducible, CsA-sensitive T cell factors, in parallel with transfection results. Authentic NFAT and NF-B targets did not compete for the META(D؉) binding factor(s). The SV40 core sequence competed for META(D؉) binding factors, but META(D؉) failed to compete for the complexes obtained with the SV40 probe. Our results, taken together, indicate that META(D؉) is a novel transcriptional enhancer element that is similar in its cell-type specificity, activation dependence, and CsA sensitivity to the NFAT element. It may be relevant to the role of MMTV in expression of Mls antigens or the induction of T cell lymphomas. Mouse mammary tumor virus (MMTV) 1 is involved in at least three different biological processes: induction of mammary adenocarcinoma, generation of thymic lymphoma, and expression of minor histocompatibility superantigens of the Mls type. The relatively large and complex long terminal repeat (LTR) is implicated in all three responses. Enhancers in the LTR activate cellular proto-oncogenes to induce tumorigenesis in mammary tumors (1). On the other hand, MMTV vari-