Evidence map›Paper›PMID 34215580›Full record

ArticleScience advances2021

Systematic dissection of transcriptional regulatory networks by genome-scale and single-cell CRISPR screens.

Rui Lopes, Kathleen Sprouffske, Caibin Sheng, Esther C H Uijttewaal, Adriana Emma Wesdorp, Jan Dahinden, Simon Wengert, Juan Diaz-Miyar, Umut Yildiz, Melusine Bleu and 18 more

Open access · goldAbstract read
In one paragraph

Article in Science advances, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 25 papers.

0numbers the graph read from it
0cells of the map it votes in
25citing papers in PubMed
1.9field-weighted citation impact, top 13% 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

25 citing papers in PubMed, 33 citations in OpenAlex.

  1. FASEB bioAdvances · 2026
    Article
  2. Article
  3. Review
  4. Article
  5. Genetic regulation of the estrogen receptor and inherited predisposition to breast cancer.Proceedings of the National Academy of Sciences of the United States of America · 2025
    Article
  6. Article
  7. Article
  8. Review
  9. Article
  10. Article
  11. Article
  12. Article
  13. Review
  14. Massively Parallel CRISPR-Based Genetic Perturbation Screening at Single-Cell Resolution.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2023
    Review
  15. Article
  16. Network-based approaches for modeling disease regulation and progression.Computational and structural biotechnology journal · 2023
    Review
  17. Article
  18. Review
  19. Review
  20. The role of single-cell genomics in human genetics.Journal of medical genetics · 2022
    Review
4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

28 authors at 3 institutions in 2 countries.

Rui LopesDisease area Oncology, Novartis Institute for Biomedical Research, CH-4002 Basel, Switzerland. rui.lopes@novartis.com giorgio.galli@novartis.com.ORCID 0000-0003-3474-676X
Kathleen SprouffskeDisease area Oncology, Novartis Institute for Biomedical Research, CH-4002 Basel, Switzerland.ORCID 0000-0001-7081-2598
Caibin ShengDisease area Oncology, Novartis Institute for Biomedical Research, CH-4002 Basel, Switzerland.ORCID 0000-0002-7706-1253
Esther C H UijttewaalDisease area Oncology, Novartis Institute for Biomedical Research, CH-4002 Basel, Switzerland.ORCID 0000-0003-3892-2820
Adriana Emma WesdorpDisease area Oncology, Novartis Institute for Biomedical Research, CH-4002 Basel, Switzerland.ORCID 0000-0001-6656-2151
Jan DahindenDisease area Oncology, Novartis Institute for Biomedical Research, CH-4002 Basel, Switzerland.
Simon WengertDisease area Oncology, Novartis Institute for Biomedical Research, CH-4002 Basel, Switzerland.ORCID 0000-0003-1271-1996
Juan Diaz-MiyarDisease area Oncology, Novartis Institute for Biomedical Research, CH-4002 Basel, Switzerland.
Umut YildizDisease area Oncology, Novartis Institute for Biomedical Research, CH-4002 Basel, Switzerland.ORCID 0000-0002-7175-362X
Melusine BleuDisease area Oncology, Novartis Institute for Biomedical Research, CH-4002 Basel, Switzerland.
Verena ApfelDisease area Oncology, Novartis Institute for Biomedical Research, CH-4002 Basel, Switzerland.
Fanny Mermet-MeillonDisease area Oncology, Novartis Institute for Biomedical Research, CH-4002 Basel, Switzerland.
Rok KreseDisease area Oncology, Novartis Institute for Biomedical Research, CH-4002 Basel, Switzerland.
Mathias EderDisease area Oncology, Novartis Institute for Biomedical Research, CH-4002 Basel, Switzerland.
André Vidas OlsenBiotech Research and Innovation Centre (BRIC), The Finsen Laboratory, Rigshospitalet, University of Copenhagen, Copenhagen, Denmark.ORCID 0000-0003-0845-4632
Philipp HoppeChemical Biology and Therapeutics, Novartis Institutes for Biomedical Research, Basel, Switzerland.
Judith KnehrChemical Biology and Therapeutics, Novartis Institutes for Biomedical Research, Basel, Switzerland.
Walter CarboneChemical Biology and Therapeutics, Novartis Institutes for Biomedical Research, Basel, Switzerland.ORCID 0000-0001-6150-8295
Rachel CuttatChemical Biology and Therapeutics, Novartis Institutes for Biomedical Research, Basel, Switzerland.ORCID 0000-0001-6019-4837
Annick WaldtChemical Biology and Therapeutics, Novartis Institutes for Biomedical Research, Basel, Switzerland.ORCID 0000-0002-4670-1588
Marc AltorferChemical Biology and Therapeutics, Novartis Institutes for Biomedical Research, Basel, Switzerland.
Ulrike NaumannChemical Biology and Therapeutics, Novartis Institutes for Biomedical Research, Basel, Switzerland.ORCID 0000-0001-7783-7675
Joachim WeischenfeldtBiotech Research and Innovation Centre (BRIC), The Finsen Laboratory, Rigshospitalet, University of Copenhagen, Copenhagen, Denmark.
Antoine deWeckDisease area Oncology, Novartis Institute for Biomedical Research, CH-4002 Basel, Switzerland.ORCID 0000-0003-0887-6771
Audrey KauffmannDisease area Oncology, Novartis Institute for Biomedical Research, CH-4002 Basel, Switzerland.
Guglielmo RomaChemical Biology and Therapeutics, Novartis Institutes for Biomedical Research, Basel, Switzerland.ORCID 0000-0002-8020-4219
Dirk SchübelerFriedrich Miescher Institute for Biomedical Research, Basel, Switzerland.ORCID 0000-0002-9229-2228
Giorgio G GalliDisease area Oncology, Novartis Institute for Biomedical Research, CH-4002 Basel, Switzerland. rui.lopes@novartis.com giorgio.galli@novartis.com.ORCID 0000-0002-9401-060X
Novartis (Switzerland) · CHUniversity of Copenhagen · DKUniversity of Basel · CH

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

Millions of putative transcriptional regulatory elements (TREs) have been cataloged in the human genome, yet their functional relevance in specific pathophysiological settings remains to be determined. This is critical to understand how oncogenic transcription factors (TFs) engage specific TREs to impose transcriptional programs underlying malignant phenotypes. Here, we combine cutting edge CRISPR screens and epigenomic profiling to functionally survey ≈15,000 TREs engaged by estrogen receptor (ER). We show that ER exerts its oncogenic role in breast cancer by engaging TREs enriched in GATA3, TFAP2C, and H3K27Ac signal. These TREs control critical downstream TFs, among which TFAP2C plays an essential role in ER-driven cell proliferation. Together, our work reveals novel insights into a critical oncogenic transcription program and provides a framework to map regulatory networks, enabling to dissect the function of the noncoding genome of cancer cells.

Indexed as

Clustered Regularly Interspaced Short Palindromic RepeatsGene Regulatory NetworksCarcinogenesisEpigenomicsGenome, HumanHumansRegulatory Elements, Transcriptional

Identifiers

PMID34215580
PMCPMC11057712
OpenAlexW3176957485

What OpenQuestion holds

Textmetadata
LicenceCC BY-NC
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.