Hepatitis C virus core protein recruits nucleolar phosphoprotein B23 and coactivator p300 to relieve the repression effect of transcriptional factor YY1 on B23 gene expression.
Hepatitis C virus (HCV) core has a pleiotropic effect on various promoters. In this study, we found that the expression of nucleolar phosphoprotein B23 was enhanced in HCV core-expressing cells and, moreover, HCV core interacts directly with the C-terminal end of B23. Using sucrose gradient centrifugation analysis and immunoprecipitation assays, HCV core was found in a large complex containing B23 and its interacting partner transcription factor YY1. Both B23 and HCV core associated with YY1 in the central GA/GK-rich and C-terminal zinc finger domain. These physical interactions between core, B23, and YY1 led to ternary complex formation that was bound to the YY1 response element. In a transient cotransfection experiment, relief of the trans-suppression activity of YY1 on the YY1-response element-driven reporter by core and B23 was found. This is also true when examining the effects of these three constructs on the B23 promoter-driven reporter. Additionally, chromatin immunoprecipitation assays indicated that a transcriptional activation complex consisting of core, together with B23, p300, and YY1, was recruited to the YY1 response element of B23 promoter, and this probably occurred through complex formation between core and these three cellular transcription regulators. This is different from the situation in the absence of core, where YY1 and histone deacetylase 1, but not B23 and p300, were associated on the YY1 element as the transcription repression complex. Together, our results indicate that HCV core can recruit B23 and p300 to relieve the repression effect of YY1 on B23 promoter activity, a property that requires the intrinsic histone acetyltransferase activity of p300. Thus, because these three core-associated cellular transcription regulators have a multitude of cellular interacting proteins and are involved in a versatility of cellular processes, the complex formation described here may partially account for the pleiotropic effects of core protein on gene expression and cellular function in HCV-infected cells.