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 prom oters, which is also a binding site for c-Myc. The c-Myc oncoprotein is imp ortant in control of cellular proliferation and differentiation, while Yin- Yang 1 (YY1) has been shown to control the expression of a number of cellul ar 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 iden tified 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-med iated up-regulation of CXCR4 promoter activity, and mutation of the YY1 bin ding 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-l-replicative cycle, by modulating both the viral fusion/entry process and viral expression.