Nucl._Acids_Res.-2015-Ramasubramanyan-3563-77.pdf (3.7 MB)
Epstein-Barr virus transcription factor Zta acts through distal regulatory elements to directly control cellular gene expression
journal contribution
posted on 2023-06-08, 20:21 authored by Sharada Ramasubramanyan, Kay OsbornKay Osborn, Rajaei Al-Mohammad, Ijiel B Naranjo Perez-Fernandez, Jianmin Zuo, Nicolae Balan, Anja Godfrey, Harshil Patel, Gordon Peters, Martin Rowe, Richard G Jenner, Alison SinclairLytic replication of the human gamma herpes virus Epstein-Barr virus (EBV) is an essential prerequisite for the spread of the virus. Differential regulation of a limited number of cellular genes has been reported in B-cells during the viral lytic replication cycle. We asked whether a viral bZIP transcription factor, Zta (BZLF1, ZEBRA, EB1), drives some of these changes. Using genome-wide chromatin immunoprecipitation coupled to next-generation DNA sequencing (ChIP-seq) we established a map of Zta interactions across the human genome. Using sensitive transcriptome analyses we identified 2263 cellular genes whose expression is significantly changed during the EBV lytic replication cycle. Zta binds 278 of the regulated genes and the distribution of binding sites shows that Zta binds mostly to sites that are distal to transcription start sites. This differs from the prevailing view that Zta activates viral genes by binding exclusively at promoter elements. We show that a synthetic Zta binding element confers Zta regulation at a distance and that distal Zta binding sites from cellular genes can confer Zta-mediated regulation on a heterologous promoter. This leads us to propose that Zta directly reprograms the expression of cellular genes through distal elements.
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Publication status
- Published
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- Published version
Journal
Nucleic Acids ResearchISSN
0305-1048Publisher
Oxford University PressExternal DOI
Issue
7Volume
43Page range
3563-3577Department affiliated with
- Biochemistry Publications
Full text available
- Yes
Peer reviewed?
- Yes
Legacy Posted Date
2015-04-22First Open Access (FOA) Date
2015-04-22First Compliant Deposit (FCD) Date
2015-04-22Usage metrics
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