Imperial College London
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ProfessorPaulFarrell

Faculty of Medicine, Department of Infectious Disease

Professor of Tumour Virology
 
 
 
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Contact

 

+44 (0)20 7594 2005p.farrell Website

 
 
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Location

 

Section of VirologyNorfolk PlaceSt Mary's Campus

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Summary

 

Publications

Citation

BibTex format

@article{Gunnell:2016:nar/gkw085,
author = {Gunnell, A and Webb, HM and Wood, CD and McClellan, MJ and Wichaidit, B and Kempkes, B and Jenner, RG and Osborne, C and Farrell, PJ and West, MJ},
doi = {nar/gkw085},
journal = {Nucleic Acids Research},
pages = {4636--4650},
title = {RUNX super-enhancer control through the Notch pathway by Epstein-Barr virus transcription factors regulates B cell growth.},
url = {http://dx.doi.org/10.1093/nar/gkw085},
volume = {44},
year = {2016}
}
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RIS format (EndNote, RefMan)

TY  - JOUR
AB  - In B cells infected by the cancer-associated Epstein-Barr virus (EBV), RUNX3 and RUNX1 transcription is manipulated to control cell growth. The EBV-encoded EBNA2 transcription factor (TF) activates RUNX3 transcription leading to RUNX3-mediated repression of the RUNX1 promoter and the relief of RUNX1-directed growth repression. We show that EBNA2 activates RUNX3 through a specific element within a -97 kb super-enhancer in a manner dependent on the expression of the Notch DNA-binding partner RBP-J. We also reveal that the EBV TFs EBNA3B and EBNA3C contribute to RUNX3 activation in EBV-infected cells by targeting the same element. Uncovering a counter-regulatory feed-forward step, we demonstrate EBNA2 activation of a RUNX1 super-enhancer (-139 to -250 kb) that results in low-level RUNX1 expression in cells refractory to RUNX1-mediated growth inhibition. EBNA2 activation of the RUNX1 super-enhancer is also dependent on RBP-J. Consistent with the context-dependent roles of EBNA3B and EBNA3C as activators or repressors, we find that these proteins negatively regulate the RUNX1 super-enhancer, curbing EBNA2 activation. Taken together our results reveal cell-type-specific exploitation of RUNX gene super-enhancers by multiple EBV TFs via the Notch pathway to fine tune RUNX3 and RUNX1 expression and manipulate B-cell growth.
AU  - Gunnell,A
AU  - Webb,HM
AU  - Wood,CD
AU  - McClellan,MJ
AU  - Wichaidit,B
AU  - Kempkes,B
AU  - Jenner,RG
AU  - Osborne,C
AU  - Farrell,PJ
AU  - West,MJ
DO  - nar/gkw085
EP  - 4650
PY  - 2016///
SN  - 1362-4962
SP  - 4636
TI  - RUNX super-enhancer control through the Notch pathway by Epstein-Barr virus transcription factors regulates B cell growth.
T2  - Nucleic Acids Research
UR  - http://dx.doi.org/10.1093/nar/gkw085
UR  - http://hdl.handle.net/10044/1/29936
VL  - 44
ER  -
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