PT  - JOURNAL ARTICLE
AU  - Andrew N. Holding
AU  - Federico M. Giorgi
AU  - Amanda Donnelly
AU  - Amy E. Cullen
AU  - Luke A. Selth
AU  - Florian Markowetz
TI  - VULCAN: Network Analysis of ER-á activation reveals reprogramming of GRHL2
AID  - 10.1101/266908
DP  - 2018 Jan 01
TA  - bioRxiv
PG  - 266908
4099  - http://biorxiv.org/content/early/2018/03/13/266908.short
4100  - http://biorxiv.org/content/early/2018/03/13/266908.full
AB  - VULCAN utilises network analysis of genome-wide DNA binding data to predict regulatory interactions of transcription factors. We benchmarked our approach against alternative methods and found improved performance in all cases. VULCAN analysis of estrogen receptor (ER) activation in breast cancer highlighted key components of the ER signalling axis and identified a novel interaction with GRHL2, validated by ChIP-seq and quantitative proteomics. Mechanistically, we show E2-responsive GRHL2 binding occurs concurrently with increases in eRNA transcription and GRHL2 negatively regulates transcription at these sites. These findings provide new insight into ER action in breast cancer and validate VULCAN as a powerful tool.AbbreviationsARAndrogen ReceptorARACNe-APAccuRate Algorithm for reConstruction of Network through Adaptive PartitioningCCLECancer Cell Line EncyclopediaChIPChromatin ImmunoPrecipitationEREstrogen Receptor-AlphaEREEstrogen-Response ElementsGSEAGene Set Enrichment AnalysisGRHL2Grainyhead Like Transcription Factor 2METABRICMolEcular TAxonomy of BReast cancer International ConsortiumPBSPhosphate Buffered SalinePIProtease InhibitorsPRProgesterone ReceptorTCGAThe Cancer Genome AtlasTFTranscription FactorVIPERVirtual Inference of Protein activity by Enriched Regulon analysisVULCANVirtUaL ChIP-Seq Analysis through Networks