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VULCAN integrates ChIP-seq with patient-derived co-expression networks to identify GRHL2 as a key co-regulator of ERa at enhancers in breast cancer. | LitMetric

AI Article Synopsis

  • VULCAN is a method that analyzes ChIP-seq data to uncover transcription factor interactions, using publicly available tumor expression data to focus on breast cancer and the estrogen receptor-alpha.
  • The analysis reveals a novel interaction between the estrogen receptor and the protein GRHL2, showing that GRHL2 impacts estrogen receptor binding and transcriptional activity.
  • Findings from this study enhance understanding of GRHL2's role in estrogen receptor signaling and underscore VULCAN's utility as a predictive tool in cancer research.

Article 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.

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Source
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6515683PMC
http://dx.doi.org/10.1186/s13059-019-1698-zDOI Listing

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