USF/c-Myc enhances, while Yin-Yang 1 suppresses, the promoter activity of CXCR4, a coreceptor for HIV-1 entry.
Transcription factors USF1 and USF2 up-regulate gene expression (i.e. , HIV-1 long terminal repeats) via interaction with an E box on their target promoters, which is also a binding site for c-Myc. The c-Myc oncoprotein is important in control of cellular proliferation and differentiation, while Yin-Yang 1 (YY1) has been shown to control the expression of a number of cellular and viral genes. These two proteins physically interact with each other and mutually inhibit their respective biological functions. In this study, we show that USF/c-Myc up-regulates, while YY1 down-regulates the promoter activity of CXCR4, a coreceptor for T cell-tropic HIV-1 entry. We have identified an E box around -260 and a YY1 binding site around -300 relative to the transcription start site. Mutation of the E box abolished USF/c-Myc-mediated up-regulation of CXCR4 promoter activity, and mutation of the YY1 binding site was associated with unresponsiveness to YY1-mediated inhibition. These data suggest that USF/c-Myc and YY1 may play an important role in the HIV-1-replicative cycle, by modulating both the viral fusion/entry process and viral expression.
Moriuchi
M
M
Laboratory of Immunoregulation, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD 20892, USA. Baltimore, MD 21201, USA.
Moriuchi
H
H
Margolis
D M
DM
Fauci
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AS
D001483:Base Sequence; D004268:DNA-Binding Proteins / Q000378:metabolism*; D050981:Erythroid-Specific DNA-Binding Factors; D015497:HIV-1 / Q000254:growth & development*; D018257:Helix-Loop-Helix Motifs; D006801:Humans; D016350:Leucine Zippers; D007963:Leukocytes, Mononuclear / Q000821:virology*; D008969:Molecular Sequence Data; D011401:Promoter Regions, Genetic; D011485:Protein Binding; D016271:Proto-Oncogene Proteins c-myc / Q000378:metabolism*; D019718:Receptors, CXCR4 / Q000096:biosynthesis / Q000235:genetics*; D013489:Suppression, Genetic; D014157:Transcription Factors / Q000378:metabolism*; D015533:Transcriptional Activation; D051720:Upstream Stimulatory Factors; D050986:YY1 Transcription Factor
D004268:DNA-Binding Proteins; D050981:Erythroid-Specific DNA-Binding Factors; D016271:Proto-Oncogene Proteins c-myc; D019718:Receptors, CXCR4; D014157:Transcription Factors; C497181:USF1 protein, human; C497184:USF2 protein, human; D051720:Upstream Stimulatory Factors; D050986:YY1 Transcription Factor; C494698:YY1 protein, human