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Epstein-Barr virus transcription factor Zta acts through distal regulatory elements to directly control cellular gene expression.

Ramasubramanyan S, Osborn K, Al-Mohammad R, Naranjo Perez-Fernandez IB, Zuo J, Balan N, Godfrey A, Patel H, Peters G, Rowe M, Jenner RG, Sinclair AJ - Nucleic Acids Res. (2015)

Bottom Line: Using genome-wide chromatin immunoprecipitation coupled to next-generation DNA sequencing (ChIP-seq) we established a map of Zta interactions across the human genome.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.

View Article: PubMed Central - PubMed

Affiliation: School of Life Sciences, University of Sussex, Brighton BN1 9QG, UK.

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Zta binding across the human genome. ChIP-Seq was undertaken with an antibody against Zta protein using chromatin from Akata BL cells induced to enter EBV lytic replication cycle by cross-linking the B-cell receptor with anti-IgG. The DNA bound by Zta was aligned to the human genome and peaks of Zta binding were identified using model-based analysis of ChIP-seq (MACS). (A) The proportions of genes associated with proximal (<2 kb from TSS), intermediate (2–4 kb) and distal (>4 kb) Zta binding sites is shown. (B) The presence of common DNA sequence motifs within the Zta binding sites was determined using MEME-ChIP. The enriched motifs are colored together with the significance of the enrichment. The related ZRE motif is shown below each in black (17).
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Figure 1: Zta binding across the human genome. ChIP-Seq was undertaken with an antibody against Zta protein using chromatin from Akata BL cells induced to enter EBV lytic replication cycle by cross-linking the B-cell receptor with anti-IgG. The DNA bound by Zta was aligned to the human genome and peaks of Zta binding were identified using model-based analysis of ChIP-seq (MACS). (A) The proportions of genes associated with proximal (<2 kb from TSS), intermediate (2–4 kb) and distal (>4 kb) Zta binding sites is shown. (B) The presence of common DNA sequence motifs within the Zta binding sites was determined using MEME-ChIP. The enriched motifs are colored together with the significance of the enrichment. The related ZRE motif is shown below each in black (17).

Mentions: Although some of the Zta binding sites (14%) were close to the annotated transcriptional start sites (TSS) of cellular genes (Figure 1B and Supplementary Table 1), analogous to the situation observed for the interaction of Zta with viral genes, the majority of the Zta binding sites (86%) were more distant (≥4 kb from the nearest TSS). By assigning each of the Zta peaks to the closest TSS, irrespective of distance, we identified 2395 cellular genes as potential candidates for regulation by Zta.


Epstein-Barr virus transcription factor Zta acts through distal regulatory elements to directly control cellular gene expression.

Ramasubramanyan S, Osborn K, Al-Mohammad R, Naranjo Perez-Fernandez IB, Zuo J, Balan N, Godfrey A, Patel H, Peters G, Rowe M, Jenner RG, Sinclair AJ - Nucleic Acids Res. (2015)

Zta binding across the human genome. ChIP-Seq was undertaken with an antibody against Zta protein using chromatin from Akata BL cells induced to enter EBV lytic replication cycle by cross-linking the B-cell receptor with anti-IgG. The DNA bound by Zta was aligned to the human genome and peaks of Zta binding were identified using model-based analysis of ChIP-seq (MACS). (A) The proportions of genes associated with proximal (<2 kb from TSS), intermediate (2–4 kb) and distal (>4 kb) Zta binding sites is shown. (B) The presence of common DNA sequence motifs within the Zta binding sites was determined using MEME-ChIP. The enriched motifs are colored together with the significance of the enrichment. The related ZRE motif is shown below each in black (17).
© Copyright Policy - creative-commons
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4402532&req=5

Figure 1: Zta binding across the human genome. ChIP-Seq was undertaken with an antibody against Zta protein using chromatin from Akata BL cells induced to enter EBV lytic replication cycle by cross-linking the B-cell receptor with anti-IgG. The DNA bound by Zta was aligned to the human genome and peaks of Zta binding were identified using model-based analysis of ChIP-seq (MACS). (A) The proportions of genes associated with proximal (<2 kb from TSS), intermediate (2–4 kb) and distal (>4 kb) Zta binding sites is shown. (B) The presence of common DNA sequence motifs within the Zta binding sites was determined using MEME-ChIP. The enriched motifs are colored together with the significance of the enrichment. The related ZRE motif is shown below each in black (17).
Mentions: Although some of the Zta binding sites (14%) were close to the annotated transcriptional start sites (TSS) of cellular genes (Figure 1B and Supplementary Table 1), analogous to the situation observed for the interaction of Zta with viral genes, the majority of the Zta binding sites (86%) were more distant (≥4 kb from the nearest TSS). By assigning each of the Zta peaks to the closest TSS, irrespective of distance, we identified 2395 cellular genes as potential candidates for regulation by Zta.

Bottom Line: Using genome-wide chromatin immunoprecipitation coupled to next-generation DNA sequencing (ChIP-seq) we established a map of Zta interactions across the human genome.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.

View Article: PubMed Central - PubMed

Affiliation: School of Life Sciences, University of Sussex, Brighton BN1 9QG, UK.

Show MeSH
Related in: MedlinePlus