Increased spacing between Sp1 and TATAA renders human immunodeficiency virus type 1 replication defective: implication for Tat function.
Expression of the human immunodeficiency virus type 1 (HIV-1) is strongly activated by Tat. The proper action of Tat requires three elements: TATAA, TAR, and upstream motifs in the HIV-1 long terminal repeat. We show here that the correct spatial arrangement among Tat, Sp1, and TATAA crucially influences HIV expression. Under conditions in which basal promoter activity is unperturbed, distancing Sp1 from TATAA markedly affected Tat trans activation. An increase in the Sp1-TATAA distance from 18 to 101 nucleotides (depending on the inserted sequence) rendered HIV-1 either partially or wholly replication defective. This critical dependence on spacing suggests that Tat-, Sp1-, and TATAA-binding factors must correctly contact each other for optimal expression and replication of HIV-1.
Huang
L M
LM
Laboratory of Molecular Microbiology, National Institute of Allergy and Infectious Diseases, Bethesda, Maryland 20892.
Jeang
K T
KT
D001483:Base Sequence; D004742:Enhancer Elements, Genetic / Q000235:genetics; D015967:Gene Expression Regulation, Viral; D015696:Gene Products, tat / Q000378:metabolism; D015497:HIV-1 / Q000235:genetics* / Q000254:growth & development; D006367:HeLa Cells; D006801:Humans; D008969:Molecular Sequence Data; D011401:Promoter Regions, Genetic / Q000235:genetics*; D016329:Sp1 Transcription Factor / Q000378:metabolism; D016385:TATA Box; D014157:Transcription Factors / Q000378:metabolism*; D014158:Transcription, Genetic; D015533:Transcriptional Activation; D014779:Virus Replication; D054322:tat Gene Products, Human Immunodeficiency Virus
D015696:Gene Products, tat; D016329:Sp1 Transcription Factor; D014157:Transcription Factors; D054322:tat Gene Products, Human Immunodeficiency Virus