Genomics

Dataset Information

162

RUNX super-enhancer control through the Notch pathway by Epstein-Barr virus transcription factors regulates B cell growth


ABSTRACT: 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. Overall design: Examination of EBNA2 protein binding using a monoclonal antibody (PE2) in single ChIP-seq experiments carried out in the human GM12878 EBV transformed lymphoblastoid cell line.

INSTRUMENT(S): Illumina Genome Analyzer IIx (Homo sapiens)

SUBMITTER: Richard Jenner  

PROVIDER: GSE76869 | GEO | 2016-03-03

SECONDARY ACCESSION(S): PRJNA308834

REPOSITORIES: GEO

altmetric image

Publications

RUNX super-enhancer control through the Notch pathway by Epstein-Barr virus transcription factors regulates B cell growth.

Gunnell Andrea A   Webb Helen M HM   Wood C David CD   McClellan Michael J MJ   Wichaidit Billy B   Kempkes Bettina B   Jenner Richard G RG   Osborne Cameron C   Farrell Paul J PJ   West Michelle J MJ  

Nucleic acids research 20160215 10


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  ...[more]

Similar Datasets

2016-08-04 | E-GEOD-82149 | ArrayExpress
2016-08-04 | E-GEOD-82148 | ArrayExpress
2011-01-06 | E-GEOD-24362 | ArrayExpress
2011-01-06 | GSE24362 | GEO
| GSE75503 | GEO
| GSE75385 | GEO
2010-12-31 | E-GEOD-21375 | ArrayExpress
| GSE88729 | GEO
2010-12-31 | GSE21375 | GEO
2013-07-31 | E-GEOD-49338 | ArrayExpress