Journal
VIROLOGY
Volume 391, Issue 2, Pages 221-231Publisher
ACADEMIC PRESS INC ELSEVIER SCIENCE
DOI: 10.1016/j.virol.2009.06.014
Keywords
KSHV/HHV-8; Zinc finger; DNA binding; Transcription repression
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Funding
- PHS [CA76903]
- NCRR COBRE [RR15635]
- NATIONAL CANCER INSTITUTE [R01CA075903, K12CA076903] Funding Source: NIH RePORTER
- NATIONAL CENTER FOR RESEARCH RESOURCES [P20RR015635] Funding Source: NIH RePORTER
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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. (C) 2009 Elsevier Inc. All rights reserved.
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