Human T cell transcription factor GATA-3 stimulates HIV-1 expression.
A family of transcriptional activating proteins, the GATA factors, has been shown to bind to a consensus motif through a highly conserved C4 zinc finger DNA binding domain. One member of this multigene family, GATA-3, is most abundantly expressed in T lymphocytes, a cellular target for human immunodeficiency virus type 1 (HIV-1) infection and replication. In vitro DNase I footprinting analysis revealed six hGATA-3 binding sites in the U3 region (the transcriptional regulatory domain) of the HIV-1 LTR. Cotransfection of an hGATA-3 expression plasmid with a reporter plasmid whose transcription is directed by the HIV-1 LTR resulted in 6- to 10-fold stimulation of LTR-mediated transcription, whereas site specific mutation of these GATA sites resulted in virtual abrogation of the activation by hGATA-3. Further, deletion of the hGATA-3 transcriptional activation domain abolished GATA-dependent HIV-1 trans-activation, showing that the stimulation of viral transcription observed is a direct effect of cotransfected hGATA-3. Introduction of the HIV-1 plasmids in which the GATA sites have been mutated into human T lymphocytes also caused a significant reduction in LTR-mediated transcription at both the basal level and in (PHA- plus PMA-) stimulated T cells. These observations suggest that in addition to its normal role in T lymphocyte gene regulation, hGATA-3 may also play a significant role in HIV-1 transcriptional activation.
Yang
Z
Z
Department of Biochemistry, Molecular Biology and Cell Biology, Northwestern University, Evanston, IL 60208-3500.
Engel
J D
JD
D000818:Animals; D001483:Base Sequence; D001665:Binding Sites; D002460:Cell Line; D004279:DNA, Viral / Q000378:metabolism; D004268:DNA-Binding Proteins / Q000235:genetics / Q000378:metabolism / Q000494:pharmacology*; D003850:Deoxyribonuclease I; D050990:GATA3 Transcription Factor; D016325:HIV Long Terminal Repeat / Q000235:genetics; D015497:HIV-1 / Q000187:drug effects / Q000235:genetics* / Q000502:physiology; D006367:HeLa Cells; D006801:Humans; D008969:Molecular Sequence Data; D016297:Mutagenesis, Site-Directed; D010835:Phytohemagglutinins / Q000494:pharmacology; D010957:Plasmids; D011784:Quail; D013601:T-Lymphocytes / Q000378:metabolism / Q000382:microbiology; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology; D015534:Trans-Activators / Q000235:genetics / Q000378:metabolism / Q000494:pharmacology*; D015533:Transcriptional Activation; D014162:Transfection
D004279:DNA, Viral; D004268:DNA-Binding Proteins; D050990:GATA3 Transcription Factor; C494749:GATA3 protein, human; D010835:Phytohemagglutinins; D015534:Trans-Activators; D003850:Deoxyribonuclease I; D013755:Tetradecanoylphorbol Acetate