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

Virology. 2009 Sep 1;391(2):221-31. doi: 10.1016/j.virol.2009.06.014. Epub 2009 Jul 9.

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.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • DNA, Viral / metabolism*
  • Gene Expression Regulation, Viral*
  • Herpesvirus 8, Human / physiology*
  • Immediate-Early Proteins / antagonists & inhibitors*
  • Promoter Regions, Genetic
  • Protein Structure, Tertiary
  • Repressor Proteins / metabolism*
  • Trans-Activators / antagonists & inhibitors*
  • Zinc Fingers

Substances

  • DNA, Viral
  • Immediate-Early Proteins
  • Repressor Proteins
  • Rta protein, Human herpesvirus 8
  • Trans-Activators
  • ZNF426 protein, human