title: Functional interactions between C/EBP, Sp1, and COUP-TF regulate human immunodeficiency virus type 1 gene transcription in human brain cells.
abstract: Human immunodeficiency virus type 1 (HIV-1) infects the central nervous system (CNS) and plays a direct role in the pathogenesis of AIDS dementia. However, mechanisms underlying HIV-1 gene expression in the CNS are poorly understood. The importance of CCAAT/enhancer binding proteins (C/EBP) for HIV-1 expression in cells of the immune system has been recently reported. In this study, we have examined the role and the molecular mechanisms by which proteins of the C/EBP family regulate HIV-1 gene transcription in human brain cells. We found that NF-IL6 acts as a potent activator of the long terminal repeat (LTR)-driven transcription in microglial and oligodendroglioma cells. In contrast, C/EBPgamma inhibits NF-IL6-induced activation. Consistent with previous data, our transient expression results show cell-type-specific NF-IL6-mediated transactivation. In glial cells, full activation needs the presence of the C/EBP binding sites; however, NF-IL6 is still able to function via the minimal -40/+80 region. In microglial cells, C/EBP sites are not essential, since NF-IL6 acts through the -68/+80 LTR region, containing two binding sites for the transcription factor Sp1. Moreover, we show that functional interactions between NF-IL6 and Sp1 lead to synergistic transcriptional activation of the LTR in oligodendroglioma and to mutual repression in microglial cells. We further demonstrate that NF-IL6 physically interacts with the nuclear receptor chicken ovalbumin upstream promoter transcription factor (COUP-TF), via its DNA binding domain, in vitro and in cells, which results in mutual transcriptional repression. These findings reveal how the interplay of NF-IL6 and C/EBPgamma, together with Sp1 and COUP-TF, regulates HIV-1 gene transcription in brain cells.
authors.affiliation: Unité 338 INSERM, 67084 Strasbourg Cedex, France.
authors.forename: C
authors.initials: C
authors.lastname: Schwartz
authors.forename: P
authors.initials: P
authors.lastname: Catez
authors.forename: O
authors.initials: O
authors.lastname: Rohr
authors.forename: D
authors.initials: D
authors.lastname: Lecestre
authors.forename: D
authors.initials: D
authors.lastname: Aunis
authors.forename: E
authors.initials: E
authors.lastname: Schaeffer
mesh_terms: D001921:Brain / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*; D022762:CCAAT-Enhancer-Binding Proteins; D051836:COUP Transcription Factors; D002460:Cell Line; D004268:DNA-Binding Proteins / Q000378:metabolism*; D016325:HIV Long Terminal Repeat; D015497:HIV-1 / Q000235:genetics*; D006801:Humans; D009457:Neuroglia / Q000187:drug effects / Q000378:metabolism; D009687:Nuclear Proteins / Q000378:metabolism*; D011485:Protein Binding; D011987:Receptors, Steroid; D016329:Sp1 Transcription Factor / Q000378:metabolism*; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology; D014157:Transcription Factors / Q000378:metabolism*; D014158:Transcription, Genetic
chemical_list: D022762:CCAAT-Enhancer-Binding Proteins; D051836:COUP Transcription Factors; D004268:DNA-Binding Proteins; D009687:Nuclear Proteins; D011987:Receptors, Steroid; D016329:Sp1 Transcription Factor; D014157:Transcription Factors; D013755:Tetradecanoylphorbol Acetate