Abstract
Background: VirtUaL 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.
Results: VULCAN 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.
Conclusions: Our 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.
Original language | English |
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Article number | 91 (2019) |
Number of pages | 16 |
Journal | GENOME BIOLOGY |
Volume | 20 |
DOIs | |
Publication status | Published - 13 May 2019 |
Externally published | Yes |
Keywords
- Breast cancer
- ChIP-seq
- Dynamics
- ER
- GRHL2
- H3K27ac
- Master regulator
- Network analysis
- P300
- VULCAN