Contribution of the TATA motif to Tat-mediated transcriptional activation of human immunodeficiency virus gene expression

Abstract

Tat-mediated transcriptional activation of human immunodeficiency virus (HIV) gene expression requires the presence of the cis-acting Tat-responsive element, TAR, and a functional enhancer-promoter element. The ability of Tat to function with heterologous enhancer sequences led us to examine the role of the minimal basal promoter for trans activation. Substitution of HIV TATA sequences (nucleotides -20 to -35) with TATA elements derived from other promoters had little effect on the basal level of transcription or the ability to activate the HIV long terminal repeat upon stimulation through upstream activation sequences. In contrast, minimal alterations within the TATA motif had a profound effect on trans activation, as demonstrated by the 3- to 10-fold reduction in activation following expression of Tat. Our findings suggest that minor changes in the TATA motif affect the composition of the initiation-elongation complex and that the composition of this complex is critical for Tat-dependent activation of gene expression.