Journal
GENOME BIOLOGY
Volume 20, Issue -, Pages -Publisher
BMC
DOI: 10.1186/s13059-019-1698-z
Keywords
Breast cancer; Network analysis; Dynamics; ER; Master regulator; ChIP-seq; VULCAN; GRHL2; P300; H3K27ac
Funding
- CRUK core grant [C14303/A17197, A19274]
- Breast Cancer Now Award [2012NovPR042]
- Alan Turing Institute under the EPSRC [EP/N510129/129/1]
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BackgroundVirtUaL ChIP-seq Analysis through Networks (VULCAN) infers regulatory interactions of transcription factors by overlaying networks generated from publicly available tumor expression data onto ChIP-seq data. We apply our method to dissect the regulation of estrogen receptor-alpha activation in breast cancer to identify potential co-regulators of the estrogen receptor's transcriptional response.ResultsVULCAN analysis of estrogen receptor activation in breast cancer highlights the key components of the estrogen receptor complex alongside a novel interaction with GRHL2. We demonstrate that GRHL2 is recruited to a subset of estrogen receptor binding sites and regulates transcriptional output, as evidenced by changes in estrogen receptor-associated eRNA expression and stronger estrogen receptor binding at active enhancers after GRHL2 knockdown.ConclusionsOur findings provide new insight into the role of GRHL2 in regulating eRNA transcription as part of estrogen receptor signaling. These results demonstrate VULCAN, available from Bioconductor, as a powerful predictive tool.
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