Network analysis of ChIP-seq data by VULCAN identifies GRHL2 as a key co-regulator of ERa in luminal breast cancer
- 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.
- Authors:
- A Holding, F Giorgi, A Donnelly, A Cullen, S Nagarajan, L Selth, F Markowetz
- Publication date:
- 1st Aug 2018
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- DOI