Evidence map›Paper›PMID 31171035›Full record

ArticleEpigenetics & chromatin2019

Human monocyte-to-macrophage differentiation involves highly localized gain and loss of DNA methylation at transcription factor binding sites.

Koen F Dekkers, Annette E Neele, J Wouter Jukema, Bastiaan T Heijmans, Menno P J de Winther

Open access · goldAbstract read
In one paragraph

Article in Epigenetics & chromatin, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 31 papers.

0numbers the graph read from it
0cells of the map it votes in
31citing papers in PubMed
2.2field-weighted citation impact, top 11% 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

31 citing papers in PubMed, 54 citations in OpenAlex.

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  14. A conciseFrontiers in cell and developmental biology · 2023
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  20. Epigenetic regulation of inflammatory factors in adipose tissue.Biochimica et biophysica acta. Molecular and cell biology of lipids · 2021
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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

5 authors at 3 institutions in 2 countries.

Koen F DekkersMolecular Epidemiology, Department of Biomedical Data Sciences, Leiden University Medical Center, Leiden, The Netherlands.
Annette E NeeleDepartment of Medical Biochemistry, Amsterdam Cardiovascular Sciences, Meibergdreef 9, Amsterdam UMC, University of Amsterdam, Amsterdam, The Netherlands.
J Wouter JukemaDepartment of Cardiology, Leiden University Medical Center, Leiden, The Netherlands.
Bastiaan T HeijmansMolecular Epidemiology, Department of Biomedical Data Sciences, Leiden University Medical Center, Leiden, The Netherlands. b.t.heijmans@lumc.nl.
Menno P J de WintherDepartment of Medical Biochemistry, Amsterdam Cardiovascular Sciences, Meibergdreef 9, Amsterdam UMC, University of Amsterdam, Amsterdam, The Netherlands. m.dewinther@amc.uva.nl.
Leiden University Medical Center · NLAmsterdam University Medical Centers · NLInstitute for Sports Medicine · DE

Funding

AMC AMC-fellowshipFondation Leducq transatlantic network grantHartstichting 2007T067Hartstichting 2010B022Hartstichting 2017T075Hartstichting CVON2011/B019Hartstichting CVON2017-20Horizon 2020 REPROGRAMSpark-Holding bv 2015B002the European Union ITN-grant EPIMAC
6 · The paper itself

Abstract

backgroundMacrophages and their precursors monocytes play a key role in inflammation and chronic inflammatory disorders. Monocyte-to-macrophage differentiation and activation programs are accompanied by significant epigenetic remodeling where DNA methylation associates with cell identity. Here we show that DNA methylation changes characteristic for monocyte-to-macrophage differentiation occur at transcription factor binding sites, and, in contrast to what was previously described, are generally highly localized and encompass both losses and gains of DNA methylation.

resultsWe compared genome-wide DNA methylation across 440,292 CpG sites between human monocytes, naïve macrophages and macrophages further activated toward a pro-inflammatory state (using LPS/IFNγ), an anti-inflammatory state (IL-4) or foam cells (oxLDL and acLDL). Moreover, we integrated these data with public whole-genome sequencing data on monocytes and macrophages to demarcate differentially methylated regions. Our analysis showed that differential DNA methylation was most pronounced during monocyte-to-macrophage differentiation, was typically restricted to single CpGs or very short regions, and co-localized with lineage-specific enhancers irrespective of whether it concerns gain or loss of methylation. Furthermore, differentially methylated CpGs were located at sites characterized by increased binding of transcription factors known to be involved in monocyte-to-macrophage differentiation including C/EBP and ETS for gain and AP-1 for loss of methylation.

conclusionOur study highlights the involvement of subtle, yet highly localized remodeling of DNA methylation at regulatory regions in cell differentiation.

Indexed as

DNA MethylationAdultBinding SitesCell DifferentiationCpG IslandsDNA-Binding ProteinsEpigenesis, GeneticFemaleGenome, HumanGenome-Wide Association StudyHumansMacrophagesMaleMonocytesProtein BindingTranscription FactorsDNA-Binding ProteinsTranscription FactorsDifferentiationDNA methylationEpigenomicsMacrophageMonocyteTranscription factor

Identifiers

PMID31171035
PMCPMC6551876
OpenAlexW2948449939

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.