Evidence map›Paper›PMID 31084623›Full record

ArticleGenome biology2019

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

Erratum issuedOpen access · goldAbstract readEvaluation Study
In one paragraph

Article in Genome biology, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. An erratum has been issued. Cited by 22 papers.

0numbers the graph read from it
0cells of the map it votes in
22citing papers in PubMed
1.7field-weighted citation impact, top 15% of its field
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

22 citing papers in PubMed, 47 citations in OpenAlex.

  1. Defining the DNA Binding Specificity of GRHL2.bioRxiv : the preprint server for biology · 2026
    Article
  2. Article
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  5. A novel NaOncogene · 2024
    Article
  6. Article
  7. Review
  8. Article
  9. Article
  10. GRHL2-controlled gene expression networks in luminal breast cancer.Cell communication and signaling : CCS · 2023
    Article
  11. Article
  12. FKBP52 and FKBP51 differentially regulate the stability of estrogen receptor in breast cancer.Proceedings of the National Academy of Sciences of the United States of America · 2022
    Article
  13. Grainyhead-like (Grhl) Target Genes in Development and Cancer.International journal of molecular sciences · 2022
    Review
  14. Roles of enhancer RNAs in sex hormone-dependent cancers.Journal of cancer research and clinical oncology · 2022
    Review
  15. Review
  16. Article
  17. Review
  18. Article
  19. Article
  20. Grainyhead-like 2 as a double-edged sword in development and cancer.American journal of translational research · 2020
    Review
4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

7 authors at 3 institutions in 3 countries.

Andrew N HoldingCRUK Cambridge Institute, University of Cambridge, Robinson Way, Cambridge, CB2 0RE, UK. anh25@cam.ac.uk.ORCID 0000-0002-8459-7048
Federico M GiorgiCRUK Cambridge Institute, University of Cambridge, Robinson Way, Cambridge, CB2 0RE, UK.
Amanda DonnellyCRUK Cambridge Institute, University of Cambridge, Robinson Way, Cambridge, CB2 0RE, UK.
Amy E CullenCRUK Cambridge Institute, University of Cambridge, Robinson Way, Cambridge, CB2 0RE, UK.
Sankari NagarajanCRUK Cambridge Institute, University of Cambridge, Robinson Way, Cambridge, CB2 0RE, UK.
Luke A SelthDame Roma Mitchell Cancer Research Laboratories and Freemasons Foundation Centre for Men's Health, Adelaide Medical School, The University of Adelaide, Adelaide, SA, Australia.
Florian MarkowetzCRUK Cambridge Institute, University of Cambridge, Robinson Way, Cambridge, CB2 0RE, UK.
University of Cambridge · GBFreemasons Foundation Centre for Men's Health · AUTuring Institute · GB

Funding

Cancer Research UK 19274Cancer Research UK A19274Cancer Research UK C14303/A17197
6 · The paper itself

Abstract

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.

Indexed as

Gene Expression Regulation, NeoplasticGenetic TechniquesAlgorithmsBreast NeoplasmsDNA-Binding ProteinsEstrogen Receptor alphaFemaleHumansTranscription FactorsDNA-Binding ProteinsEstrogen Receptor alphaGRHL2 protein, humanTranscription FactorsBreast cancerChIP-seqDynamicsERGRHL2H3K27acMaster regulatorNetwork analysisP300VULCAN

Identifiers

PMID31084623
PMCPMC6515683
OpenAlexW2939964476

What OpenQuestion holds

Textmetadata
LicenceCC BY
Read underepoch 390

Registered trials

None linked

Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.