TFII-I regulates induction of chromosomally integrated human immunodeficiency virus type 1 long terminal repeat in cooperation with USF.
Human immunodeficiency virus type 1 (HIV-1) replication is coupled to T-cell activation through its dependence on host cell transcription factors. Despite the enormous sequence variability of these factors, several cis elements for host factors are highly conserved within the 5' long terminal repeats (LTRs) of viruses from AIDS patients; among these is the RBEIII upstream element for the Ras response element binding factor 2 (RBF-2). Here we show that RBF-2 is comprised of a USF1/USF2 heterodimer and TFII-I, which bind cooperatively to RBEIII. Recombinant USF1/USF2 binds to the RBEIII core sequence 160-fold less efficiently than it binds to an E box element, but the interaction with RBEIII is stimulated by TFII-I. Chromosomally integrated HIV-1 LTRs bearing an RBEIII mutation have slightly elevated basal transcription in unstimulated Jurkat cells but are unresponsive to cross-linking of the T-cell receptor or stimulation with phorbol myristate acetate (PMA) and ionomycin. Induction is inhibited by dominant interfering USF and TFII-I but not by the dominant negative I-kappaB protein. USF1, USF2, and TFII-I bind to the integrated wild-type LTR in unstimulated cells and become phosphorylated during the induction of transcription upon stimulation with PMA. These results demonstrate that USF1/USF2 and TFII-I interact cooperatively at the upstream RBEIII element and are necessary for the induction of latent HIV-1 in response to T-cell activation signals.
Chen
Jiguo
J
Department of Biochemistry and Molecular Biology, University of British Columbia, Vancouver, BC, V6T 1Z3, Canada.
Malcolm
Tom
T
Estable
Mario C
MC
Roeder
Robert G
RG
Sadowski
Ivan
I
D000818:Animals; D019556:COS Cells; D004268:DNA-Binding Proteins / Q000378:metabolism*; D019281:Dimerization; D024202:Electrophoretic Mobility Shift Assay; D015967:Gene Expression Regulation, Viral; D016325:HIV Long Terminal Repeat / Q000502:physiology*; D015497:HIV-1 / Q000235:genetics* / Q000502:physiology; D006801:Humans; D019169:Jurkat Cells; D008213:Lymphocyte Activation; D010766:Phosphorylation; D011485:Protein Binding; D011948:Receptors, Antigen, T-Cell / Q000502:physiology; D013601:T-Lymphocytes / Q000276:immunology / Q000821:virology*; D014157:Transcription Factors / Q000378:metabolism*; D019473:Transcription Factors, TFII / Q000378:metabolism*; D014158:Transcription, Genetic; D051720:Upstream Stimulatory Factors; D014775:Virus Activation; D016662:Virus Integration; D014779:Virus Replication
D004268:DNA-Binding Proteins; C104259:GTF2I protein, human; D011948:Receptors, Antigen, T-Cell; D014157:Transcription Factors; D019473:Transcription Factors, TFII; C497181:USF1 protein, human; C497184:USF2 protein, human; D051720:Upstream Stimulatory Factors