The cellular YY1 transcription factor binds a cis-acting, negatively regulating element in the Epstein-Barr virus BRLF1 promoter.
Disruption of Epstein-Barr virus latency is induced by expression of either the BZLF1 (in B cells and epithelial cells) or BRLF1 (in epithelial cells only) immediate-early protein. Regulation of BZLF1 and BRLF1 transcription may therefore modulate the stringency of viral latency. The cellular transcription factor YY1 negatively regulates BZLF1 transcription. Here we show that the BRLF1 promoter (Rp) sequences from -206 to -227 (relative to the mRNA start site) and from -7 to +6 are directly bound by YY1. Mutation of the upstream YY1 binding site increases constitutive Rp activity in epithelial cells and B cells, while mutation of the downstream YY1 binding site does not significantly affect Rp activity. Negative regulation of BZLF1 and BRLF1 transcription by YY1 may act to maintain viral latency.
Zalani
S
S
Lineberger Comprehensive Cancer Center, University of North Carolina at Chapel Hill, 27599-7295, USA.
Coppage
A
A
Holley-Guthrie
E
E
Kenney
S
S
D001665:Binding Sites; D004279:DNA, Viral / Q000378:metabolism; D004268:DNA-Binding Proteins / Q000235:genetics / Q000378:metabolism*; D050981:Erythroid-Specific DNA-Binding Factors; D006367:HeLa Cells; D004854:Herpesvirus 4, Human / Q000235:genetics / Q000378:metabolism*; D006801:Humans; D017874:Immediate-Early Proteins / Q000235:genetics*; D016297:Mutagenesis, Site-Directed; D011401:Promoter Regions, Genetic; D011993:Recombinant Fusion Proteins / Q000235:genetics / Q000378:metabolism; D012045:Regulatory Sequences, Nucleic Acid; D015534:Trans-Activators; D014157:Transcription Factors / Q000235:genetics* / Q000378:metabolism*; D014407:Tumor Cells, Cultured; D014764:Viral Proteins; D050986:YY1 Transcription Factor
C068382:BRLF1 protein, Human herpesvirus 4; D004279:DNA, Viral; D004268:DNA-Binding Proteins; D050981:Erythroid-Specific DNA-Binding Factors; D017874:Immediate-Early Proteins; D011993:Recombinant Fusion Proteins; D015534:Trans-Activators; D014157:Transcription Factors; D014764:Viral Proteins; D050986:YY1 Transcription Factor; C494698:YY1 protein, human