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bioRxiv · 10.1101/266908

Network Dynamics of ER-α activation reveals reprogramming of GRHL2

Holding, A.·Giorgi, F. M.·Donnelly, A.·Cullen, A. E.·Selth, L. A.·Markowetz, F.
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Abstract

VULCAN infers regulatory interactions of transcription factors by overlaying networks generated from tumor expression data onto ChIP-seq data. VULCAN analysis of estrogen receptor (ER) activation in breast cancer highlighted key components of the ER complex alongside a novel interaction with GRHL2. We demonstrate that GRHL2 is recruited to a subset of ER binding sites and regulates the transcriptional output of ER, as evidenced by: changes in ER-associated eRNA expression; and stronger ER binding at active enhancers (H3K27ac sites) after GRHL2 knockdown. Our findings provide new insight into ER signaling and demonstrate VULCAN, available from Bioconductor, as a powerful predictive tool.

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Holding, A., Giorgi, F. M., Donnelly, A., Cullen, A. E., Selth, L. A., Markowetz, F.. 2018-02-16. Network Dynamics of ER-α activation reveals reprogramming of GRHL2. https://doi.org/10.1101/266908

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