Evidence map›Paper›PMID 34599190›Full record

ArticleNature communications2021

Enhancer-associated H3K4 methylation safeguards in vitro germline competence.

Tore Bleckwehl, Giuliano Crispatzu, Kaitlin Schaaf, Patricia Respuela, Michaela Bartusel, Laura Benson, Stephen J Clark, Kristel M Dorighi, Antonio Barral, Magdalena Laugsch and 5 more

Abstract 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 26 papers.

0numbers the graph read from it
0cells of the map it votes in
26citing papers in PubMed
–field-weighted citation impact
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

26 citing papers in PubMed.

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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

15 authors.

Tore BleckwehlCenter for Molecular Medicine Cologne (CMMC), University of Cologne, Cologne, Germany. tbleckwe@uni-koeln.de.ORCID 0000-0003-1116-0512
Giuliano CrispatzuCenter for Molecular Medicine Cologne (CMMC), University of Cologne, Cologne, Germany.ORCID 0000-0001-8041-2125
Kaitlin SchaafCenter for Molecular Medicine Cologne (CMMC), University of Cologne, Cologne, Germany.
Patricia RespuelaCenter for Molecular Medicine Cologne (CMMC), University of Cologne, Cologne, Germany.
Michaela BartuselCenter for Molecular Medicine Cologne (CMMC), University of Cologne, Cologne, Germany.ORCID 0000-0003-1008-1951
Laura BensonEpigenetics Programme, Babraham Institute, Cambridge, UK.ORCID 0000-0002-7239-6126
Stephen J ClarkEpigenetics Programme, Babraham Institute, Cambridge, UK.ORCID 0000-0002-6183-491X
Kristel M DorighiDepartment of Chemical and Systems Biology, Stanford University School of Medicine, Stanford, USA.
Antonio BarralCentro Nacional de Investigaciones Cardiovasculares (CNIC), Madrid, Spain.
Magdalena LaugschCenter for Molecular Medicine Cologne (CMMC), University of Cologne, Cologne, Germany.
Wilfred F J van IJckenErasmus University Medical Center Rotterdam, Center for Biomics, Rotterdam, the Netherlands.ORCID 0000-0002-0421-8301
Miguel ManzanaresCentro Nacional de Investigaciones Cardiovasculares (CNIC), Madrid, Spain.ORCID 0000-0003-4849-2836
Joanna WysockaDepartment of Chemical and Systems Biology, Stanford University School of Medicine, Stanford, USA.ORCID 0000-0002-6909-6544
Wolf ReikEpigenetics Programme, Babraham Institute, Cambridge, UK.ORCID 0000-0003-0216-9881
Álvaro Rada-IglesiasCenter for Molecular Medicine Cologne (CMMC), University of Cologne, Cologne, Germany. alvaro.rada@unican.es.ORCID 0000-0001-7137-1341

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

Germline specification in mammals occurs through an inductive process whereby competent cells in the post-implantation epiblast differentiate into primordial germ cells (PGC). The intrinsic factors that endow epiblast cells with the competence to respond to germline inductive signals remain unknown. Single-cell RNA sequencing across multiple stages of an in vitro PGC-like cells (PGCLC) differentiation system shows that PGCLC genes initially expressed in the naïve pluripotent stage become homogeneously dismantled in germline competent epiblast like-cells (EpiLC). In contrast, the decommissioning of enhancers associated with these germline genes is incomplete. Namely, a subset of these enhancers partly retain H3K4me1, accumulate less heterochromatic marks and remain accessible and responsive to transcriptional activators. Subsequently, as in vitro germline competence is lost, these enhancers get further decommissioned and lose their responsiveness to transcriptional activators. Importantly, using H3K4me1-deficient cells, we show that the loss of this histone modification reduces the germline competence of EpiLC and decreases PGCLC differentiation efficiency. Our work suggests that, although H3K4me1 might not be essential for enhancer function, it can facilitate the (re)activation of enhancers and the establishment of gene expression programs during specific developmental transitions.

Indexed as

Enhancer Elements, GeneticAnimalsCell DifferentiationChromatinEmbryo, MammalianGene Expression RegulationGerm CellsGerm LayersHistonesLysineMaleMethylationMiceMice, TransgenicMouse Embryonic Stem CellsMutationChromatinHistonesLysineOtx2 protein, mouseOtx Transcription Factors

Identifiers

PMID34599190
PMCPMC8486853

What OpenQuestion holds

Textmetadata
LicenceCC BY
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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.