Structural basis of DNA methylation-dependent site selectivity of the Epstein-Barr virus lytic switch protein ZEBRA/Zta/BZLF1.
Nucleic Acids Res
; 50(1): 490-511, 2022 01 11.
Article
en En
| MEDLINE
| ID: mdl-34893887
ABSTRACT
In infected cells, Epstein-Barr virus (EBV) alternates between latency and lytic replication. The viral bZIP transcription factor ZEBRA (Zta, BZLF1) regulates this cycle by binding to two classes of ZEBRA response elements (ZREs) CpG-free motifs resembling the consensus AP-1 site recognized by cellular bZIP proteins and CpG-containing motifs that are selectively bound by ZEBRA upon cytosine methylation. We report structural and mutational analysis of ZEBRA bound to a CpG-methylated ZRE (meZRE) from a viral lytic promoter. ZEBRA recognizes the CpG methylation marks through a ZEBRA-specific serine and a methylcytosine-arginine-guanine triad resembling that found in canonical methyl-CpG binding proteins. ZEBRA preferentially binds the meZRE over the AP-1 site but mutating the ZEBRA-specific serine to alanine inverts this selectivity and abrogates viral replication. Our findings elucidate a DNA methylation-dependent switch in ZEBRA's transactivation function that enables ZEBRA to bind AP-1 sites and promote viral latency early during infection and subsequently, under appropriate conditions, to trigger EBV lytic replication by binding meZREs.
Texto completo:
1
Bases de datos:
MEDLINE
Asunto principal:
Proteínas Virales
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ADN Viral
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Transactivadores
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Herpesvirus Humano 4
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Infecciones por Virus de Epstein-Barr
Límite:
Humans
Idioma:
En
Revista:
Nucleic Acids Res
Año:
2022
Tipo del documento:
Article
País de afiliación:
Francia