Functional roles for the TATA promoter and enhancers in basal and Tat-induced expression of the human immunodeficiency virus type 1 long terminal repeat.
We have analyzed the contributory role of the human immunodeficiency virus type 1 (HIV-1) promoter and enhancers in basal and Tat-induced transcription. We found that a minimal promoter competent for basal expression is contained within sequences spanning nucleotides -43 to +80. Basal expression from this HIV-1 promoter was boosted more by the additional presence of the NF-kappa B elements than by the Sp1 elements. The minimal long terminal repeat promoter (-43 to +80), while having an intact TAR sequence, was not Tat inducible. However, the simple addition of short synthetic enhancer motifs (AP1, Oct, Sp1, and NF-kappa B) conferred Tat responsiveness. This ability to respond to Tat was in part dependent on the presence of the HIV-1 promoter. Changing the HIV-1 TATA to other eucaryotic TATA or non-TATA initiators minimally affected basal expression but altered Tat inducibility. Our findings suggest a specific context of functional promoter and enhancer elements that is optimal for Tat trans activation of the HIV-1 long terminal repeat. Our results do not allow conclusions about whether Tat acts at the level of initiation or at the level of elongation to be drawn.
Berkhout
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B
Laboratory of Molecular Microbiology, National Institute of Allergy and Infectious Diseases, Bethesda, Maryland 20892.
Jeang
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KT
D001483:Base Sequence; D002478:Cells, Cultured; D004279:DNA, Viral; D004742:Enhancer Elements, Genetic; D015967:Gene Expression Regulation, Viral; D015696:Gene Products, tat / Q000378:metabolism*; D016325:HIV Long Terminal Repeat / Q000235:genetics*; D015497:HIV-1 / Q000235:genetics*; D008969:Molecular Sequence Data; D011401:Promoter Regions, Genetic; D016385:TATA Box; D014158:Transcription, Genetic; D015533:Transcriptional Activation / Q000235:genetics; D054322:tat Gene Products, Human Immunodeficiency Virus
D004279:DNA, Viral; D015696:Gene Products, tat; D054322:tat Gene Products, Human Immunodeficiency Virus