Evidence map›Paper›PMID 25619691›Full record

ArticleCell2015

Ligand-dependent enhancer activation regulated by topoisomerase-I activity.

Janusz Puc, Piotr Kozbial, Wenbo Li, Yuliang Tan, Zhijie Liu, Tom Suter, Kenneth A Ohgi, Jie Zhang, Aneel K Aggarwal, Michael G Rosenfeld

Erratum issuedOpen access · bronzeAbstract read
In one paragraph

Article in Cell, 2015. 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 89 papers.

0numbers the graph read from it
0cells of the map it votes in
89citing papers in PubMed
11.4field-weighted citation impact, top 1% 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

89 citing papers in PubMed, 140 citations in OpenAlex.

  1. Article
  2. Article
  3. DNA topological regulation in RNA polymerase II transcription.Cellular & molecular biology letters · 2026
    Review
  4. Article
  5. Review
  6. Article
  7. Article
  8. Article
  9. Article
  10. Article
  11. Article
  12. Article
  13. Review
  14. Article
  15. Article
  16. Article
  17. Article
  18. Article
  19. Article
  20. Review

29 more citing papers are in PubMed but not listed here.

4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

10 authors at 2 institutions in 1 country.

Janusz PucHoward Hughes Medical Institute, Department of Medicine, School of Medicine, University of California, San Diego, La Jolla, CA 92093-0648, USA.
Piotr KozbialHoward Hughes Medical Institute, Department of Medicine, School of Medicine, University of California, San Diego, La Jolla, CA 92093-0648, USA.
Wenbo LiHoward Hughes Medical Institute, Department of Medicine, School of Medicine, University of California, San Diego, La Jolla, CA 92093-0648, USA.
Yuliang TanHoward Hughes Medical Institute, Department of Medicine, School of Medicine, University of California, San Diego, La Jolla, CA 92093-0648, USA.
Zhijie LiuHoward Hughes Medical Institute, Department of Medicine, School of Medicine, University of California, San Diego, La Jolla, CA 92093-0648, USA.
Tom SuterHoward Hughes Medical Institute, Department of Medicine, School of Medicine, University of California, San Diego, La Jolla, CA 92093-0648, USA; Division of Biological Sciences, Department of Molecular Biology, University of California, San Diego, La Jolla, CA 92093-0648, USA.
Kenneth A OhgiHoward Hughes Medical Institute, Department of Medicine, School of Medicine, University of California, San Diego, La Jolla, CA 92093-0648, USA.
Jie ZhangHoward Hughes Medical Institute, Department of Medicine, School of Medicine, University of California, San Diego, La Jolla, CA 92093-0648, USA.
Aneel K AggarwalDepartment of Structural and Chemical Biology, Icahn School of Medicine at Mount Sinai, New York, NY 10029, USA.
Michael G RosenfeldHoward Hughes Medical Institute, Department of Medicine, School of Medicine, University of California, San Diego, La Jolla, CA 92093-0648, USA. Electronic address: mrosenfeld@ucsd.edu.
Howard Hughes Medical Institute · USIcahn School of Medicine at Mount Sinai · US

Funding

VIRAL MALIGNANCYP30CA023100 · NCI · UNIVERSITY OF CALIFORNIA, SAN DIEGO · PI Jesse Nodora · 1985 to 2026
$124.9M
Transcriptional Genomics CoreP01DK074868 · NIDDK · UNIVERSITY OF CALIFORNIA, SAN DIEGO · PI ROSENFELD, MICHAEL G · 2007 to 2016
$16.6M
HORMONAL AND DEVELOPMENTAL REGULATION OF GENE EXPRESSIONR01DK018477 · NIDDK · UNIVERSITY OF CALIFORNIA, SAN DIEGO · PI ROSENFELD, MICHAEL G · 1986 to 2025
$12.7M
REGULATION OF NEUROENDOCRINE SWITCHING EVENTSR37DK039949 · NIDDK · UNIVERSITY OF CALIFORNIA, SAN DIEGO · PI ROSENFELD, MICHAEL G · 1987 to 2020
$12.3M
EXPANSION OF NURSA TRANSCRIPTOMINE ANNOTATIONU24DK097748 · NIDDK · BAYLOR COLLEGE OF MEDICINE · PI EVANS, RONALD M, MCKENNA, NEIL · 2012 to 2017
$9.2M
Ligand Regulated Epigenetic/Nuclear Architectural Strategies and Human DiseaseR01NS034934 · NINDS · UNIVERSITY OF CALIFORNIA, SAN DIEGO · PI ROSENFELD, MICHAEL G · 1995 to 2013
$6.8M
Enhancer TherapyR01CA173903 · NCI · UNIVERSITY OF CALIFORNIA, SAN DIEGO · PI GLASS, CHRISTOPHER K · 2012 to 2016
$6.3M
MOLECULAR MECHANISMS OF AORTIC AND PULMONARY DEFECTSR01HL065445 · NHLBI · UNIVERSITY OF CALIFORNIA, SAN DIEGO · PI ROSENFELD, MICHAEL G · 2000 to 2014
$5.3M
Repressors in Prostate CancerR01CA097134 · NCI · UNIVERSITY OF CALIFORNIA, SAN DIEGO · PI ROSENFELD, MICHAEL G · 2002 to 2012
$3.2M
New Methods to Uncover Global Transcriptional Programs for Disease Risk VariantsR01GM104459 · NIGMS · ALBERT EINSTEIN COLLEGE OF MEDICINE, INC · PI SUH, YOUSIN · 2013 to 2016
$2.5M
REGULATION OF NEUROENDOCRINE SWITCHING EVENTSR01DK039949 · NIDDK · UNIVERSITY OF CALIFORNIA, SAN DIEGO · PI ROSENFELD, MICHAEL G · 1996 to 2024
$2.4M
Regulated Retrotransposon Elements in Neuroendocrine SystemK01DK080180 · NIDDK · UNIVERSITY OF CALIFORNIA, SAN DIEGO · PI PUC, JANUSZ ADAM · 2007 to 2009
$301k
Howard Hughes Medical InstituteNCI NIH HHS CA173903NCI NIH HHS P30 CA023100NCI NIH HHS R01 CA097134NCI NIH HHS R01 CA173903NHLBI NIH HHS HL065445NHLBI NIH HHS R01 HL065445NIDDK NIH HHS DK018477NIDDK NIH HHS DK039949NIDDK NIH HHS DK074868NIDDK NIH HHS DK097748NIDDK NIH HHS K01 DK080180NIDDK NIH HHS K01DK080180NIDDK NIH HHS P01 DK074868NIDDK NIH HHS R01 DK018477NIDDK NIH HHS R01 DK039949NIDDK NIH HHS R37 DK039949NIDDK NIH HHS U24 DK097748NIGMS NIH HHS GM104459NIGMS NIH HHS R01 GM104459NINDS NIH HHS NS034934NINDS NIH HHS R01 NS034934
6 · The paper itself

Abstract

The discovery that enhancers are regulated transcription units, encoding eRNAs, has raised new questions about the mechanisms of their activation. Here, we report an unexpected molecular mechanism that underlies ligand-dependent enhancer activation, based on DNA nicking to relieve torsional stress from eRNA synthesis. Using dihydrotestosterone (DHT)-induced binding of androgen receptor (AR) to prostate cancer cell enhancers as a model, we show rapid recruitment, within minutes, of DNA topoisomerase I (TOP1) to a large cohort of AR-regulated enhancers. Furthermore, we show that the DNA nicking activity of TOP1 is a prerequisite for robust eRNA synthesis and enhancer activation and is kinetically accompanied by the recruitment of ATR and the MRN complex, followed by additional components of DNA damage repair machinery to the AR-regulated enhancers. Together, our studies reveal a linkage between eRNA synthesis and ligand-dependent TOP1-mediated nicking-a strategy exerting quantitative effects on eRNA expression in regulating AR-bound enhancer-dependent transcriptional programs.

Indexed as

Enhancer Elements, GeneticGene Expression RegulationCell Line, TumorDNA-Binding ProteinsDNA Breaks, Single-StrandedDNA RepairDNA Topoisomerases, Type IGene Knockdown TechniquesHomeodomain ProteinsHumansMRE11 Homologue ProteinReceptors, AndrogenTranscription FactorsTranscription, GeneticDNA-Binding ProteinsDNA Topoisomerases, Type IHomeodomain ProteinsMRE11 Homologue ProteinMRE11 protein, humanNKX3-1 protein, humanReceptors, AndrogenTranscription Factors

Identifiers

PMID25619691
PMCPMC4422651
OpenAlexW2062702286

What OpenQuestion holds

Textmetadata
LicenceTDM
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.