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
| Autor: | Florian Markowetz, Amy E Cullen, Sankari Nagarajan, Andrew N Holding, Federico M. Giorgi, Amanda Donnelly, Luke A. Selth |
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| Přispěvatelé: | Holding, Andrew N., Giorgi, Federico M., Donnelly, Amanda, Cullen, Amy E., Nagarajan, Sankari, Selth, Luke A., Markowetz, Florian, Holding, Andrew N [0000-0002-8459-7048], Apollo - University of Cambridge Repository |
| Rok vydání: | 2019 |
| Předmět: |
Master regulator
lcsh:QH426-470 VULCAN Regulator GRHL2 Breast Neoplasms Computational biology Biology 03 medical and health sciences 0302 clinical medicine Breast cancer medicine Humans P300 Enhancer lcsh:QH301-705.5 030304 developmental biology 0303 health sciences Estrogen Receptor alpha medicine.disease H3K27ac Dynamics ChIP-seq DNA-Binding Proteins Gene Expression Regulation Neoplastic lcsh:Genetics Coexpression ChIP-Seq RNA-Seq Bioinformatics GRHL2 Breast Cancer Gene Networks lcsh:Biology (General) ER Genetic Techniques Key (cryptography) Network analysis Female 030217 neurology & neurosurgery Algorithms Transcription Factors |
| Zdroj: | Holding, A N, Giorgi, F M, Donnelly, A, Cullen, A E, Nagarajan, S, Selth, L A & Markowetz, F 2019, ' 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 ', Genome biology, vol. 20, no. 1 . https://doi.org/10.1186/s13059-019-1698-z Genome Biology, Vol 20, Iss 1, Pp 1-16 (2019) |
| ISSN: | 1474-760X |
| DOI: | 10.17863/cam.39608 |
| Popis: | BackgroundVirtUaL 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.ResultsVULCAN 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.ConclusionsOur 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. |
| Databáze: | OpenAIRE |
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