NF-kappaB-repressing factor inhibits elongation of human immunodeficiency virus type 1 transcription by DRB sensitivity-inducing factor.
Human immunodeficiency virus type 1 (HIV-1) is able to establish a latent infection during which the integrated provirus remains transcriptionally silent. In response to specific stimuli, the HIV-1 long terminal repeat (LTR) is highly activated, enhancing both transcriptional initiation and elongation. Here, we have identified a specific binding sequence of the nuclear NF-kappaB-repressing factor (NRF) within the HIV-1 LTR. The aim of this work was to define the role of NRF in regulating the LTR. Our data show that the endogenous NRF is required for transcriptional activation of the HIV-1 LTR in stimulated cells. In unstimulated cells, however, NRF inhibits HIV-1 LTR activity at the level of transcription elongation. Binding of NRF to the LTR in unstimulated cells prevents recruitment of elongation factor DRB sensitivity-inducing factor and formation of processive elongation complexes by hyperphosphorylated RNA polymerase II. Our data suggest that NRF interrupts the regulatory coupling of LTR binding factors and transcription elongation events. This inhibitory mechanism might contribute to transcriptional quiescence of integrated HIV-1 provirus.
Dreikhausen
Ursula
U
Institute of Pharmacology, Medical School Hannover, Germany.
Hiebenthal-Millow
Kirsten
K
Bartels
Myriam
M
Resch
Klaus
K
Nourbakhsh
Mahtab
M
D001483:Base Sequence; D002460:Cell Line; D004268:DNA-Binding Proteins / Q000235:genetics / Q000378:metabolism*; D004004:Dichlororibofuranosylbenzimidazole / Q000494:pharmacology; D015967:Gene Expression Regulation, Viral / Q000187:drug effects / Q000235:genetics*; D016325:HIV Long Terminal Repeat / Q000235:genetics*; D015497:HIV-1 / Q000187:drug effects / Q000235:genetics*; D006801:Humans; D009154:Mutation / Q000235:genetics; D009687:Nuclear Proteins / Q000378:metabolism*; D012097:Repressor Proteins / Q000235:genetics / Q000378:metabolism*; D014157:Transcription Factors / Q000235:genetics / Q000378:metabolism*; D014158:Transcription, Genetic / Q000187:drug effects / Q000235:genetics*; D035602:Transcriptional Elongation Factors
D004268:DNA-Binding Proteins; C111027:NKRF protein, human; D009687:Nuclear Proteins; D012097:Repressor Proteins; C112224:SUPT5H protein, human; D014157:Transcription Factors; D035602:Transcriptional Elongation Factors; D004004:Dichlororibofuranosylbenzimidazole