PT  - JOURNAL ARTICLE
AU  - Andrew N. Holding
AU  - Federico M. Giorgi
AU  - Amanda Donnelly
AU  - Amy E. Cullen
AU  - Sankari Nagarajan
AU  - Luke A Selth
AU  - Florian Markowetz
TI  - 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
AID  - 10.1101/266908
DP  - 2019 Jan 01
TA  - bioRxiv
PG  - 266908
4099  - http://biorxiv.org/content/early/2019/04/21/266908.short
4100  - http://biorxiv.org/content/early/2019/04/21/266908.full
AB  - 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 applied our method to dissect the regulation of Estrogen Receptor-alpha (ER) activation in breast cancer to identify potential coregulators of the ER’s transcriptional response.Results VULCAN analysis of 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.Conclusions Our findings provide new insight into the role of GRHL2 in regulating eRNA transcription as part of ER signaling. These results demonstrate VULCAN, available from Bioconductor, as a powerful predictive tool.ARAndrogen ReceptorARACNe-APAccuRate Algorithm for reConstruction of Network through Adaptive PartitioningCCLECancer Cell Line EncyclopediaChIPChromatin ImmunoPrecipitationE2EstradiolEREstrogen Receptor-AlphaEREEstrogen Response ElementseRNAEnhancer RNAGSEAGene Set Enrichment AnalysisGRHL2Grainyhead Like Transcription Factor 2METABRICMolEcular TAxonomy of BReast cancer International Consortium PBS Phosphate Buffered SalinePIProtease InhibitorsPRProgesterone ReceptorTCGAThe Cancer Genome AtlasTFTranscription FactorVIPERVirtual Inference of Protein activity by Enriched Regulon analysis VULCAN VirtUaL ChIP-seq Analysis through Networks