An activation-dependent, T-lymphocyte-specific transcriptional activator in the mouse mammary tumor virus env gene.
Transcription of the complete mouse mammary tumor virus (MMTV) proviral genome in mouse cells is controlled by a strong promoter in its long terminal repeat. In the mouse T lymphoma EL4, there is a second, activation-dependent transcriptional initiation site within the envelope (env) gene, from which a short mRNA is generated, encoding the open reading frame of the long terminal repeat. We now report the isolation of a segment of the MMTV env gene (called META, for MMTV env transcriptional activator) which has the expected transcription-activating properties seen in EL4.E1 cells. Namely, it induces activation-dependent, T-lymphocyte-specific transcription of a chloramphenicol acetyltransferase reporter gene. It is active in mouse or human T-helper lymphocyte lines when they are stimulated to transcribe lymphokine genes but is inactive in unstimulated T-helper cells, fibroblasts, a cytotoxic T-lymphocyte line, and a mastocytoma cell line. Its activity is inhibited by cyclosporin A, a specific inhibitor of lymphokine transcription. Several forms of the META have been isolated from EL4.E1 cells, a mouse T-helper cell hybridoma, and from BALB/c spleen cells. Linked to the heterologous thymidine kinase promoter, a 400-bp portion of it is an inducible, orientation-independent, and cyclosporin A-sensitive transcriptional activator in T-helper cells.
Miller
C L
CL
Department of Biochemistry, University of Alberta, Edmonton, Canada.
Garner
R
R
Paetkau
V
V
D000818:Animals; D001483:Base Sequence; D002478:Cells, Cultured; D015500:Chloramphenicol O-Acetyltransferase / Q000235:genetics; D015972:Gene Expression Regulation, Neoplastic; D015752:Genes, env / Q000235:genetics*; D008213:Lymphocyte Activation; D008325:Mammary Neoplasms, Experimental / Q000235:genetics; D008324:Mammary Tumor Virus, Mouse / Q000235:genetics*; D051379:Mice; D008969:Molecular Sequence Data; D011533:Proviruses / Q000235:genetics; D011994:Recombinant Proteins / Q000235:genetics; D012045:Regulatory Sequences, Nucleic Acid / Q000235:genetics; D012689:Sequence Homology, Nucleic Acid; D013601:T-Lymphocytes / Q000382:microbiology*; D014158:Transcription, Genetic / Q000235:genetics*
D011994:Recombinant Proteins; D015500:Chloramphenicol O-Acetyltransferase