Evidence map›Paper›PMID 25737282›Full record

ArticleGenes & development2015

The KRAB zinc finger protein ZFP809 is required to initiate epigenetic silencing of endogenous retroviruses.

Gernot Wolf, Peng Yang, Annette C Füchtbauer, Ernst-Martin Füchtbauer, Andreia M Silva, Chungoo Park, Warren Wu, Anders L Nielsen, Finn S Pedersen, Todd S Macfarlan

Open access · diamondAbstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Genes & development, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 120 papers.

0numbers the graph read from it
0cells of the map it votes in
120citing 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

120 citing papers in PubMed, 181 citations in OpenAlex.

  1. Trial
  2. Article
  3. The Many Faces of SetDB1.Epigenomes · 2026
    Review
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  6. Article
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  10. Review
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  17. Article
  18. Human endogenous retroviruses and exogenous viral infections.Frontiers in cellular and infection microbiology · 2024
    Review
  19. Review
  20. Article

60 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

10 authors at 3 institutions in 2 countries.

Gernot WolfThe Eunice Kennedy Shriver National Institute of Child Health and Human Development, The National Institutes of Health, Bethesda, Maryland 20892, USA; Department of Molecular Biology and Genetics, Aarhus University, 8000 Aarhus C, Denmark;
Peng YangThe Eunice Kennedy Shriver National Institute of Child Health and Human Development, The National Institutes of Health, Bethesda, Maryland 20892, USA;
Annette C FüchtbauerDepartment of Molecular Biology and Genetics, Aarhus University, 8000 Aarhus C, Denmark;
Ernst-Martin FüchtbauerDepartment of Molecular Biology and Genetics, Aarhus University, 8000 Aarhus C, Denmark;
Andreia M SilvaDepartment of Molecular Biology and Genetics, Aarhus University, 8000 Aarhus C, Denmark;
Chungoo ParkThe Eunice Kennedy Shriver National Institute of Child Health and Human Development, The National Institutes of Health, Bethesda, Maryland 20892, USA;
Warren WuThe Eunice Kennedy Shriver National Institute of Child Health and Human Development, The National Institutes of Health, Bethesda, Maryland 20892, USA;
Anders L NielsenDepartment of Biomedicine, Aarhus University, 8000 Aarhus C, Denmark.
Finn S PedersenDepartment of Molecular Biology and Genetics, Aarhus University, 8000 Aarhus C, Denmark;
Todd S MacfarlanThe Eunice Kennedy Shriver National Institute of Child Health and Human Development, The National Institutes of Health, Bethesda, Maryland 20892, USA; todd.macfarlan@nih.gov.
Aarhus University · DKEunice Kennedy Shriver National Institute of Child Health and Human Development · USNational Institutes of Health · US

Funding

High-throughput targeted mutagenesis of mouse stem cell linesU01HG004080 · NHGRI · CHILDREN'S HOSPITAL & RES CTR AT OAKLAND · PI DE JONG, PIETER J. · 2006 to 2010
$28.1M
Production of Targeted Null Mutations for 10,000 Genes in C57BL/6 ES CellsU01HG004085 · NHGRI · REGENERON PHARMACEUTICALS, INC. · PI VALENZUELA, DAVID MANUEL · 2006 to 2010
$25.3M
Mechanisms of Mammalian Epigenome ReprogrammingZIAHD008933 · NICHD · EUNICE KENNEDY SHRIVER NATIONAL INSTITUTE OF CHILD HEALTH & HUMAN DEVELOPMENT · PI MACFARLAN, TODD SCOTT · 2013 to 2025
$19.1M
UCD KOMP PROJECT REPOSITORYU42RR024244 · NCRR · UNIVERSITY OF CALIFORNIA AT DAVIS · PI LLOYD, KC KENT · 2007 to 2010
$7.9M
NCRR NIH HHS U42 RR024244NCRR NIH HHS U42RR024244NHGRI NIH HHS U01 HG004080NHGRI NIH HHS U01HG004080NHGRI NIH HHS U01 HG004085NHGRI NIH HHS U01HG004085NICHD NIH HHS HD008933Wellcome Trust
6 · The paper itself

Abstract

Retroviruses have been invading mammalian germlines for millions of years, accumulating in the form of endogenous retroviruses (ERVs) that account for nearly one-tenth of the mouse and human genomes. ERVs are epigenetically silenced during development, yet the cellular factors recognizing ERVs in a sequence-specific manner remain elusive. Here we demonstrate that ZFP809, a member of the Krüppel-associated box zinc finger protein (KRAB-ZFP) family, initiates the silencing of ERVs in a sequence-specific manner via recruitment of heterochromatin-inducing complexes. ZFP809 knockout mice display highly elevated levels of ZFP809-targeted ERVs in somatic tissues. ERV reactivation is accompanied by an epigenetic shift from repressive to active histone modifications but only slight destabilization of DNA methylation. Importantly, using conditional alleles and rescue experiments, we demonstrate that ZFP809 is required to initiate ERV silencing during embryonic development but becomes largely dispensable in somatic tissues. Finally, we show that the DNA-binding specificity of ZFP809 is evolutionarily conserved in the Muroidea superfamily of rodents and predates the endogenization of retroviruses presently targeted by ZFP809 in Mus musculus. In sum, these data provide compelling evidence that ZFP809 evolved to recognize foreign DNA and establish histone modification-based epigenetic silencing of ERVs.

Indexed as

Epigenesis, GeneticGene SilencingAnimalsBinding SitesDNA-Binding ProteinsEmbryo, MammalianEndogenous RetrovirusesGenomeHistonesMiceMice, KnockoutProtein BindingVirus ActivationVirus IntegrationDNA-Binding ProteinsHistonesZFP809 protein, mouseendogenous retrovirusepigenetic silencingKRAB zinc finger proteinsretrovirus restriction factors

Identifiers

PMID25737282
PMCPMC4358406
OpenAlexW1964001756

What OpenQuestion holds

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LicenceCC BY-NC
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.