Network analysis of ChIP-seq data by VULCAN identifies GRHL2 as a key co-regulator of ERa in luminal breast cancer

Autor: Andrew N Holding, Amanda Donnelly, Federico M. Giorgi, Sankari Nagarajan, Luke A. Selth, Amy E Cullen, Florian Markowetz
Jazyk: angličtina
Rok vydání: 2018
Předmět:
DOI: 10.1101/266908
Popis: 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.
Databáze: OpenAIRE