The zinc finger DNA-binding domain of K-RBP plays an important role in regulating Kaposi’s sarcoma-associated herpesvirus RTA-mediated gene expression

Authors

Zhilong Yang, University of Nebraska–Lincoln
Hui-Ju Wen, University of Nebraska–Lincoln
Veenu Minhas, University of Nebraska-LincolnFollow
Charles Wood, University of Nebraska-LincolnFollow

Document Type

Article

Date of this Version

2009

Comments

Published in Virology 391:2 (September 1, 2009), pp. 221-231; doi: 10.1016/j.virol.2009.06.014 Copyright © 2009 Elsevier Inc. Used by permission.

Abstract

K-RBP is a KRAB-containing zinc finger protein with multiple zinc finger motifs and represses Kaposi’s sarcoma-associated herpesvirus (KSHV) transactivator RTA-mediated transactivation of several viral lytic gene promoters, including the ORF57 promoter. Whether K-RBP binds DNA through its zinc fingers and the role of zinc finger domain in repressing gene expression are unclear. Here we report that K-RBP binds DNA through its zinc finger domain and the target DNA sequences contain high GC content. Furthermore, K-RBP binds to KSHV ORF57 promoter, which contains a GC-rich motif. K-RBP suppresses the basal ORF57 promoter activity as well as RTA-mediated activation. The zinc finger domain of K-RBP is sufficient for the suppression of ORF57 promoter activation mediated by the viral transactivator RTA. Finally, we show that K-RBP inhibits RTA binding to ORF57 promoter. These findings suggest that the DNA-binding activity of K-RBP plays an important role in repressing viral promoter activity.