Imperial College London


Faculty of MedicineDepartment of Infectious Disease

Professor of Tumour Virology



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




Section of VirologyNorfolk PlaceSt Mary's Campus






BibTex format

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 = {},
volume = {44},
year = {2016}

RIS format (EndNote, RefMan)

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 -
UR -
VL - 44
ER -