Human transcription factor YY1 represses human immunodeficiency virus type 1 transcription and virion production.
The transcriptional activity of human immunodeficiency virus type 1 (HIV-1) is affected by many cellular factors. Homologies near the HIV-1 initiator region to the DNA-binding sequences of YY1, a multifunctional transcription factor known to regulate diverse viral and cellular promoters, suggested that YY1 might regulate HIV-1. Antibody to YY1 blocked the formation of complexes by HeLa cell nuclear extract and a DNA oligonucleotide encoding the HIV-1 initiator region. HIV-1 long terminal repeat (LTR) expression, as measured the expression of a transfected LTR-CAT reporter gene, was repressed more than 12-fold by the cotransfection of a YY1 expression vector. HIV-1 production by both COS-1 and CEM cells after transfection of an infectious molecular HIV-1 clone was repressed 7- to 20-fold by cotransfection of a YY1 expression vector. HIV-1 production was also decreased threefold in a CD4-positive lymphocyte cell line chronically infected with HIV-1 (8E5) after transfection of YY1. In situ hybridization studies confirmed that YY1 reduced HIV-1 RNA expression. YY1 may play an important role in the regulation of HIV-1 LTR expression in vivo and virus production by infected cells.
Margolis
D M
DM
Program in Molecular Medicine, University of Massachusetts Medical Center, Worcester 01605.
Somasundaran
M
M
Green
M R
MR
D000818:Animals; D001483:Base Sequence; D002460:Cell Line; D015500:Chloramphenicol O-Acetyltransferase / Q000096:biosynthesis; D004268:DNA-Binding Proteins / Q000276:immunology / Q000494:pharmacology*; D050981:Erythroid-Specific DNA-Binding Factors; D015967:Gene Expression Regulation, Viral / Q000187:drug effects*; D016655:HIV Core Protein p24 / Q000096:biosynthesis; D016325:HIV Long Terminal Repeat / Q000235:genetics*; D015497:HIV-1 / Q000235:genetics* / Q000254:growth & development; D006801:Humans; D017403:In Situ Hybridization; D008221:Lymphoid Tissue / Q000382:microbiology; D008969:Molecular Sequence Data; D011485:Protein Binding; D012333:RNA, Messenger / Q000302:isolation & purification; D012367:RNA, Viral / Q000302:isolation & purification; D011993:Recombinant Fusion Proteins / Q000096:biosynthesis; D014157:Transcription Factors / Q000276:immunology / Q000494:pharmacology*; D014158:Transcription, Genetic / Q000187:drug effects*; D014771:Virion / Q000254:growth & development; D050986:YY1 Transcription Factor
D004268:DNA-Binding Proteins; D050981:Erythroid-Specific DNA-Binding Factors; D016655:HIV Core Protein p24; D012333:RNA, Messenger; D012367:RNA, Viral; D011993:Recombinant Fusion Proteins; D014157:Transcription Factors; D050986:YY1 Transcription Factor; C494698:YY1 protein, human; D015500:Chloramphenicol O-Acetyltransferase