Evidence map›Paper›PMID 27231886›Full record

ArticlePloS one2016

Topoisomerase 1 Regulates Gene Expression in Neurons through Cleavage Complex-Dependent and -Independent Mechanisms.

Angela M Mabb, Jeremy M Simon, Ian F King, Hyeong-Min Lee, Lin-Kun An, Benjamin D Philpot, Mark J Zylka

Open access · goldAbstract read
In one paragraph

Article in PloS one, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 37 papers.

0numbers the graph read from it
0cells of the map it votes in
37citing papers in PubMed
3.3field-weighted citation impact, top 8% 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

37 citing papers in PubMed, 46 citations in OpenAlex.

  1. A multispecies toolkit ofProceedings of the National Academy of Sciences of the United States of America · 2026
    Article
  2. Article
  3. Article
  4. The Roles of Topoisomerases in Transcriptional Regulation.International journal of molecular sciences · 2026
    Review
  5. Article
  6. Article
  7. Article
  8. Topoisomerase 1 is required for the development and function of thymus.Journal of immunology (Baltimore, Md. : 1950) · 2025
    Article
  9. Article
  10. Article
  11. Article
  12. Article
  13. Article
  14. Article
  15. Article
  16. Article
  17. Topoisomerases in Immune Cell Development and Function.Journal of immunology (Baltimore, Md. : 1950) · 2023
    Review
  18. Review
  19. Article
  20. MiR-124 synergism with ELAVL3 enhances target gene expression to promote neuronal maturity.Proceedings of the National Academy of Sciences of the United States of America · 2021
    Article
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

7 authors at 2 institutions in 2 countries.

Angela M MabbDepartment of Cell Biology and Physiology, UNC Neuroscience Center, Carolina Institute for Developmental Disabilities, The University of North Carolina, Chapel Hill, North Carolina, United States of America.
Jeremy M SimonDepartment of Cell Biology and Physiology, UNC Neuroscience Center, Carolina Institute for Developmental Disabilities, The University of North Carolina, Chapel Hill, North Carolina, United States of America.
Ian F KingDepartment of Cell Biology and Physiology, UNC Neuroscience Center, Carolina Institute for Developmental Disabilities, The University of North Carolina, Chapel Hill, North Carolina, United States of America.
Hyeong-Min LeeDepartment of Cell Biology and Physiology, UNC Neuroscience Center, Carolina Institute for Developmental Disabilities, The University of North Carolina, Chapel Hill, North Carolina, United States of America.
Lin-Kun AnSchool of Pharmaceutical Sciences, Sun Yat-sen University, Guangzhou, China.
Benjamin D PhilpotDepartment of Cell Biology and Physiology, UNC Neuroscience Center, Carolina Institute for Developmental Disabilities, The University of North Carolina, Chapel Hill, North Carolina, United States of America.
Mark J ZylkaDepartment of Cell Biology and Physiology, UNC Neuroscience Center, Carolina Institute for Developmental Disabilities, The University of North Carolina, Chapel Hill, North Carolina, United States of America.
University of North Carolina at Chapel Hill · USSun Yat-sen University · CN

Funding

UNC MRDD Research CenterP30HD003110 · NICHD · UNIV OF NORTH CAROLINA CHAPEL HILL · PI PIVEN, JOSEPH · 1985 to 2012
$28.7M
UNC Neuroscience Center Research Cores: MicroscopyP30NS045892 · NINDS · UNIV OF NORTH CAROLINA CHAPEL HILL · PI ZYLKA, MARK J. · 2003 to 2022
$11.5M
Postdoctoral Research in Neurodevelopmental DisordersT32HD040127 · NICHD · UNIV OF NORTH CAROLINA CHAPEL HILL · PI BENJAMIN D PHILPOT, Mark D Shen · 2001 to 2026
$8.5M
Preclinical CoreU54HD079124 · NICHD · UNIV OF NORTH CAROLINA CHAPEL HILL · PI BELGER, AYSENIL · 2013 to 2019
$8.0M
The Elongation Hypothesis of AutismDP1ES024088 · NIEHS · UNIV OF NORTH CAROLINA CHAPEL HILL · PI ZYLKA, MARK J. · 2013 to 2017
$3.8M
Epigenetic Regulation of Ube3a as a Treatment for Angelman SyndromeR01MH093372 · NIMH · UNIV OF NORTH CAROLINA CHAPEL HILL · PI PHILPOT, BENJAMIN D, ZYLKA, MARK J. · 2012 to 2016
$3.2M
NICHD NIH HHS P30 HD003110NICHD NIH HHS T32 HD040127NICHD NIH HHS U54 HD079124NIEHS NIH HHS DP1 ES024088NIMH NIH HHS R01 MH093372NINDS NIH HHS P30 NS045892
6 · The paper itself

Abstract

Topoisomerase 1 (TOP1) inhibitors, including camptothecin and topotecan, covalently trap TOP1 on DNA, creating cleavage complexes (cc's) that must be resolved before gene transcription and DNA replication can proceed. We previously found that topotecan reduces the expression of long (>100 kb) genes and unsilences the paternal allele of Ube3a in neurons. Here, we sought to evaluate overlap between TOP1cc-dependent and -independent gene regulation in neurons. To do this, we utilized Top1 conditional knockout mice, Top1 knockdown, the CRISPR-Cas9 system to delete Top1, TOP1 catalytic inhibitors that do not generate TOP1cc's, and a TOP1 mutation (T718A) that stabilizes TOP1cc's. We found that topotecan treatment significantly alters the expression of many more genes, including long neuronal genes, immediate early genes, and paternal Ube3a, when compared to Top1 deletion. Our data show that topotecan has a stronger effect on neuronal transcription than Top1 deletion, and identifies TOP1cc-dependent and -independent contributions to gene expression.

Indexed as

Gene Expression RegulationAnimalsDNADNA Topoisomerases, Type IFemaleGene Knockout TechniquesMiceMice, Inbred C57BLNeuronsSynapsesTopotecanUbiquitin-Protein LigasesDNADNA Topoisomerases, Type ITopotecanUbe3a protein, mouseUbiquitin-Protein Ligases

Identifiers

PMID27231886
PMCPMC4883752
OpenAlexW2399950674

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.