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

Andrew N. Holding, Federico M. Giorgi, Amanda Donnelly, Amy E. Cullen, Sankari Nagarajan, Luke A. Selth, Florian Markowetz

Research output: Contribution to journalArticlepeer-review

7 Citations (Scopus)
1 Downloads (Pure)

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 languageEnglish
Article number91 (2019)
Number of pages16
JournalGENOME BIOLOGY
Volume20
DOIs
Publication statusPublished - 13 May 2019
Externally publishedYes

Keywords

  • Breast cancer
  • ChIP-seq
  • Dynamics
  • ER
  • GRHL2
  • H3K27ac
  • Master regulator
  • Network analysis
  • P300
  • VULCAN

Fingerprint Dive into the research topics of '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'. Together they form a unique fingerprint.

Cite this