Evidence map›Paper›PMID 33692344›Full record

ArticleNature communications2021

The epigenetic pioneer EGR2 initiates DNA demethylation in differentiating monocytes at both stable and transient binding sites.

Karina Mendes, Sandra Schmidhofer, Julia Minderjahn, Dagmar Glatz, Claudia Kiesewetter, Johanna Raithel, Julia Wimmer, Claudia Gebhard, Michael Rehli

Open access · goldAbstract read
In one paragraph

Article in Nature communications, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 20 papers.

0numbers the graph read from it
0cells of the map it votes in
20citing papers in PubMed
3.7field-weighted citation impact, top 6% 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

20 citing papers in PubMed, 53 citations in OpenAlex.

  1. Article
  2. EpiBrain: the brain's epigenetic landscape in a snapshot.bioRxiv : the preprint server for biology · 2026
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  4. Manual Therapy Improves Fibromyalgia Symptoms by DownregulatingInternational journal of molecular sciences · 2024
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  13. Role of TET dioxygenases in the regulation of both normal and pathological hematopoiesis.Journal of experimental & clinical cancer research : CR · 2022
    Review
  14. Article
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  17. DissectingCancers · 2022
    Review
  18. Article
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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 3 institutions in 3 countries.

Karina MendesDepartment of Internal Medicine III, University Hospital Regensburg, 93053, Regensburg, Germany.
Sandra SchmidhoferDepartment of Internal Medicine III, University Hospital Regensburg, 93053, Regensburg, Germany.
Julia MinderjahnDepartment of Internal Medicine III, University Hospital Regensburg, 93053, Regensburg, Germany.
Dagmar GlatzDepartment of Internal Medicine III, University Hospital Regensburg, 93053, Regensburg, Germany.
Claudia KiesewetterDepartment of Internal Medicine III, University Hospital Regensburg, 93053, Regensburg, Germany.
Johanna RaithelRegensburg Centre for Interventional Immunology, University Hospital Regensburg, 93053, Regensburg, Germany.
Julia WimmerDepartment of Internal Medicine III, University Hospital Regensburg, 93053, Regensburg, Germany.
Claudia GebhardRegensburg Centre for Interventional Immunology, University Hospital Regensburg, 93053, Regensburg, Germany.
Michael RehliDepartment of Internal Medicine III, University Hospital Regensburg, 93053, Regensburg, Germany. michael.rehli@ukr.de.ORCID 0000-0003-3992-932X
University Hospital Regensburg · DEHôpital Maisonneuve-Rosemont · CAUniversidade Católica Portuguesa · PT

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

The differentiation of human blood monocytes (MO), the post-mitotic precursors of macrophages (MAC) and dendritic cells (moDC), is accompanied by the active turnover of DNA methylation, but the extent, consequences and mechanisms of DNA methylation changes remain unclear. Here, we profile and compare epigenetic landscapes during IL-4/GM-CSF-driven MO differentiation across the genome and detect several thousand regions that are actively demethylated during culture, both with or without accompanying changes in chromatin accessibility or transcription factor (TF) binding. We further identify TF that are globally associated with DNA demethylation processes. While interferon regulatory factor 4 (IRF4) is found to control hallmark dendritic cell functions with less impact on DNA methylation, early growth response 2 (EGR2) proves essential for MO differentiation as well as DNA methylation turnover at its binding sites. We also show that ERG2 interacts with the 5mC hydroxylase TET2, and its consensus binding sequences show a characteristic DNA methylation footprint at demethylated sites with or without detectable protein binding. Our findings reveal an essential role for EGR2 as epigenetic pioneer in human MO and suggest that active DNA demethylation can be initiated by the TET2-recruiting TF both at stable and transient binding sites.

Indexed as

Binding SitesCells, CulturedChromatin Immunoprecipitation SequencingDNA DemethylationDNA MethylationEarly Growth Response Protein 2HumansImmunoblottingImmunoprecipitationMass SpectrometryMonocytesProtein BindingRNA-SeqEarly Growth Response Protein 2EGR2 protein, human

Identifiers

PMID33692344
PMCPMC7946903
OpenAlexW3133572143

What OpenQuestion holds

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Registered trials

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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.