Evidence map›Paper›PMID 27266524›Full record

ArticleThe EMBO journal2016

Continual removal of H3K9 promoter methylation by Jmjd2 demethylases is vital for ESC self-renewal and early development.

Marianne Terndrup Pedersen, Susanne Marije Kooistra, Aliaksandra Radzisheuskaya, Anne Laugesen, Jens Vilstrup Johansen, Daniel Geoffrey Hayward, Jakob Nilsson, Karl Agger, Kristian Helin

2 registry-linked trialsOpen access · bronzeAbstract read
In one paragraph

Article in The EMBO journal, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It is linked to 2 registered trials, which are not on this map. Cited by 77 papers.

0numbers the graph read from it
0cells of the map it votes in
77citing papers in PubMed
7.0field-weighted citation impact, top 3% 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.

NCT03070262 phase3unknown statusnot on this mapstarted 2017, after this paper: background citation

Caffeic Acid for Advanced Esophageal Squamous Cell Cancer: A Randomized, Double-blind, and Multicenter Trial in Chinese Patients

TypeinterventionalSponsorThe First Affiliated Hospital of Henan University of Science and TechnologyRan2017 to 2021Enrolled300ConditionsEsophagus CancerArmsCA, placebo group
NCT04648917 phase3unknown statusnot on this mapstarted 2019, after this paper: background citation

GASC1 Inhibitor Caffeic Acid for Advanced Squamous Esophageal Cell Cancer (ESCC): a Multicenter, Phase II Trial (GiCAEC)

TypeinterventionalSponsorThe First Affiliated Hospital of Henan University of Science and TechnologyRan2019 to 2022Enrolled80ConditionsEsophagus Cancer, Stage IIIArmsCaffeic acid
3 · Its place in the literature

Who cites it

77 citing papers in PubMed, 112 citations in OpenAlex.

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  7. Automated Image-Based Profiling of Pluripotent Stem Cell Colonies.bioRxiv : the preprint server for biology · 2025
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  8. Article
  9. Review
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  15. Coupling of stemness maintenance with cell cycle control in stem cells.Frontiers in cell and developmental biology · 2025
    Review
  16. Article
  17. Article
  18. Review
  19. Article
  20. Article

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

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

9 authors at 1 institution in 1 country.

Marianne Terndrup PedersenBiotech Research and Innovation Centre (BRIC), University of Copenhagen, Copenhagen, Denmark Centre for Epigenetics, University of Copenhagen, Copenhagen, Denmark.
Susanne Marije KooistraBiotech Research and Innovation Centre (BRIC), University of Copenhagen, Copenhagen, Denmark Centre for Epigenetics, University of Copenhagen, Copenhagen, Denmark.
Aliaksandra RadzisheuskayaBiotech Research and Innovation Centre (BRIC), University of Copenhagen, Copenhagen, Denmark Centre for Epigenetics, University of Copenhagen, Copenhagen, Denmark.
Anne LaugesenBiotech Research and Innovation Centre (BRIC), University of Copenhagen, Copenhagen, Denmark Centre for Epigenetics, University of Copenhagen, Copenhagen, Denmark The Danish Stem Cell Center (Danstem), Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark.
Jens Vilstrup JohansenBiotech Research and Innovation Centre (BRIC), University of Copenhagen, Copenhagen, Denmark.
Daniel Geoffrey HaywardThe Novo Nordisk Foundation Center for Protein Research, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark.
Jakob NilssonThe Novo Nordisk Foundation Center for Protein Research, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark.
Karl AggerBiotech Research and Innovation Centre (BRIC), University of Copenhagen, Copenhagen, Denmark Centre for Epigenetics, University of Copenhagen, Copenhagen, Denmark.
Kristian HelinBiotech Research and Innovation Centre (BRIC), University of Copenhagen, Copenhagen, Denmark Centre for Epigenetics, University of Copenhagen, Copenhagen, Denmark The Danish Stem Cell Center (Danstem), Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark kristian.helin@bric.ku.dk.ORCID 0000-0003-1975-6097
University of Copenhagen · DK

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

Chromatin-associated proteins are essential for the specification and maintenance of cell identity. They exert these functions through modulating and maintaining transcriptional patterns. To elucidate the functions of the Jmjd2 family of H3K9/H3K36 histone demethylases, we generated conditional Jmjd2a/Kdm4a, Jmjd2b/Kdm4b and Jmjd2c/Kdm4c/Gasc1 single, double and triple knockout mouse embryonic stem cells (ESCs). We report that while individual Jmjd2 family members are dispensable for ESC maintenance and embryogenesis, combined deficiency for specifically Jmjd2a and Jmjd2c leads to early embryonic lethality and impaired ESC self-renewal, with spontaneous differentiation towards primitive endoderm under permissive culture conditions. We further show that Jmjd2a and Jmjd2c both localize to H3K4me3-positive promoters, where they have widespread and redundant roles in preventing accumulation of H3K9me3 and H3K36me3. Jmjd2 catalytic activity is required for ESC maintenance, and increased H3K9me3 levels in knockout ESCs compromise the expression of several Jmjd2a/c targets, including genes that are important for ESC self-renewal. Thus, continual removal of H3K9 promoter methylation by Jmjd2 demethylases represents a novel mechanism ensuring transcriptional competence and stability of the pluripotent cell identity.

Indexed as

Promoter Regions, GeneticAnimalsEmbryonic Stem CellsHistone DemethylasesHistonesJumonji Domain-Containing Histone DemethylasesMethylationMiceMice, KnockoutHistone DemethylasesHistonesJMJD2A protein, mouseJmjd2c protein, mouseJumonji Domain-Containing Histone Demethylasesdevelopmentepigeneticshistone demethylationKdm4transcription

Identifiers

PMID27266524
PMCPMC4899663
OpenAlexW2412898159

What OpenQuestion holds

Textmetadata
Read underepoch 390

Registered trials

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.