title: HIV-1 core promoter lacks a simple initiator element but contains a bipartite activator at the transcription start site.
abstract: The human immunodeficiency virus type 1 (HIV-1) core promoter region, extending approximately from nucleotides -40 to +80 relative to the transcription start site, contains a complex array of putative regulatory elements, including a TATA box, an initiator element, an element between the TATA box and start site, binding sites for LBP/UBP, the TAR element, and others. However, because of this elaborate architecture, the precise boundaries and functional roles for the individual regulatory elements have not been defined. To facilitate a detailed analysis of the HIV-1 core promoter, we employed in vitro transcription assays to identify the simplest control elements that activate RNA synthesis in the context of a synthetic, heterologous promoter. Because mutations at the start site previously were shown to diminish transcription, we anticipated finding an initiator as a basic regulator. However, we have demonstrated that the HIV-1 core promoter lacks an initiator that is functionally analogous to those found in the terminal transferase and adenovirus major late promoters. In its place, we identified two elements between -6 and +30, both of which appear to be necessary for significant transcriptional activation. Unlike a strong initiator, the activity of these elements was dependent on the presence of a TATA box and on their position relative to TATA. We have called the region containing these two elements the HIV-1 SSR to distinguish it from the simple transcriptional initiator elements found in other genes.
authors.affiliation: Howard Hughes Medical Institute, University of California School of Medicine, Los Angeles 90024.
authors.forename: B
authors.initials: B
authors.lastname: Zenzie-Gregory
authors.forename: P
authors.initials: P
authors.lastname: Sheridan
authors.forename: K A
authors.initials: KA
authors.lastname: Jones
authors.forename: S T
authors.initials: ST
authors.lastname: Smale
mesh_terms: D001483:Base Sequence; D002478:Cells, Cultured; D004279:DNA, Viral / Q000235:genetics / Q000378:metabolism; D004268:DNA-Binding Proteins / Q000378:metabolism; D005814:Genes, Viral; D016325:HIV Long Terminal Repeat; D015497:HIV-1 / Q000235:genetics*; D006367:HeLa Cells; D006801:Humans; D008969:Molecular Sequence Data; D009838:Oligodeoxyribonucleotides; D011401:Promoter Regions, Genetic / Q000235:genetics*; D016385:TATA Box; D014158:Transcription, Genetic
chemical_list: D004279:DNA, Viral; D004268:DNA-Binding Proteins; D009838:Oligodeoxyribonucleotides