Evidence map›Paper›PMID 29351814›Full record

ArticleGenome biology2018

SETDB1 prevents TET2-dependent activation of IAP retroelements in naïve embryonic stem cells.

Özgen Deniz, Lorenzo de la Rica, Kevin C L Cheng, Dominik Spensberger, Miguel R Branco

Open access · goldAbstract read
In one paragraph

Article in Genome biology, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 18 papers.

0numbers the graph read from it
0cells of the map it votes in
18citing papers in PubMed
4.0field-weighted citation impact, top 5% 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

18 citing papers in PubMed, 55 citations in OpenAlex.

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  3. Histone methyltransferase SETDB1 safeguards mouse fetal hematopoiesis by suppressing activation of cryptic enhancers.Proceedings of the National Academy of Sciences of the United States of America · 2024
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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 1 country.

Özgen DenizBlizard Institute, Barts and The London School of Medicine and Dentistry, QMUL, London, E1 2AT, UK.
Lorenzo de la RicaBlizard Institute, Barts and The London School of Medicine and Dentistry, QMUL, London, E1 2AT, UK.
Kevin C L ChengBlizard Institute, Barts and The London School of Medicine and Dentistry, QMUL, London, E1 2AT, UK.
Dominik SpensbergerDepartment of Haematology, Cambridge Institute for Medical Research, University of Cambridge, Cambridge, CB2 0XY, UK.
Miguel R BrancoBlizard Institute, Barts and The London School of Medicine and Dentistry, QMUL, London, E1 2AT, UK. m.branco@qmul.ac.uk.
Queen Mary University of London · GBBabraham Institute · GBRoyal Society · GB

Funding

FP7 People: Marie-Curie Actions 608765FP7 People: Marie-Curie Actions () 608765Wellcome TrustWellcome Trust (GB) 101225/Z/13/Z
6 · The paper itself

Abstract

backgroundEndogenous retroviruses (ERVs), which are responsible for 10% of spontaneous mouse mutations, are kept under control via several epigenetic mechanisms. The H3K9 histone methyltransferase SETDB1 is essential for ERV repression in embryonic stem cells (ESCs), with DNA methylation also playing an important role. It has been suggested that SETDB1 protects ERVs from TET-dependent DNA demethylation, but the relevance of this mechanism for ERV expression remains unclear. Moreover, previous studies have been performed in primed ESCs, which are not epigenetically or transcriptionally representative of preimplantation embryos.

resultsWe use naïve ESCs to investigate the role of SETDB1 in ERV regulation and its relationship with TET-mediated DNA demethylation. Naïve ESCs show an increased dependency on SETDB1 for ERV silencing when compared to primed ESCs, including at the highly mutagenic intracisternal A particles (IAPs). We find that in the absence of SETDB1, TET2 activates IAP elements in a catalytic-dependent manner. Surprisingly, TET2 does not drive changes in DNA methylation levels at IAPs, suggesting that it regulates these retrotransposons indirectly. Instead, SETDB1 depletion leads to a TET2-dependent loss of H4R3me2s, which is indispensable for IAP silencing during epigenetic reprogramming.

conclusionsOur results demonstrate a novel and unexpected role for SETDB1 in protecting IAPs from TET2-dependent histone arginine demethylation.

Indexed as

Genes, Intracisternal A-ParticleAnimalsCell LineDioxygenasesDNADNA-Binding ProteinsEmbryonic Stem CellsEndogenous RetrovirusesEpigenesis, GeneticHistone CodeHistone-Lysine N-MethyltransferaseHistonesMiceProto-Oncogene ProteinsDioxygenasesDNADNA-Binding ProteinsHistone-Lysine N-MethyltransferaseHistonesProto-Oncogene ProteinsSETDB1 protein, mouseTet2 protein, mouseDNA methylationEmbryonic stem cellsHistone arginine methylationIntracisternal A particles (IAPs)RetrotransposonsSETDB1Ten-eleven translocation enzymes

Identifiers

PMID29351814
PMCPMC5775534
OpenAlexW2756679114

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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.