Evidence map›Paper›PMID 34857746›Full record

ArticleNature communications2021

Repression of germline genes by PRC1.6 and SETDB1 in the early embryo precedes DNA methylation-mediated silencing.

Kentaro Mochizuki, Jafar Sharif, Kenjiro Shirane, Kousuke Uranishi, Aaron B Bogutz, Sanne M Janssen, Ayumu Suzuki, Akihiko Okuda, Haruhiko Koseki, Matthew C Lorincz

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 35 papers.

0numbers the graph read from it
0cells of the map it votes in
35citing 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

35 citing papers in PubMed, 61 citations in OpenAlex.

  1. The Many Faces of SetDB1.Epigenomes · 2026
    Review
  2. Mechanisms of human germ cell development.Nature reviews. Molecular cell biology · 2026
    Review
  3. Article
  4. Review
  5. Article
  6. Article
  7. Article
  8. Article
  9. Article
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  12. Polycomb function in early mouse development.Cell death and differentiation · 2025
    Review
  13. Article
  14. Article
  15. Article
  16. Article
  17. DNMT1 can induce primary germ layer differentiation through de novo DNA methylation.Genes to cells : devoted to molecular & cellular mechanisms · 2024
    Article
  18. Epigenetic priming in the male germline.Current opinion in genetics & development · 2024
    Review
  19. Review
  20. Article
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 5 institutions in 2 countries.

Kentaro MochizukiDepartment of Medical Genetics, Life Sciences Institute, University of British Columbia, Vancouver, British Columbia, Canada.ORCID http://orcid.org/0000-0002-7624-9350
Jafar SharifLaboratory for Developmental Genetics, RIKEN Center for Integrative Medical Sciences (IMS), Yokohama, Kanagawa, Japan.
Kenjiro ShiraneDepartment of Medical Genetics, Life Sciences Institute, University of British Columbia, Vancouver, British Columbia, Canada.ORCID http://orcid.org/0000-0002-8528-7404
Kousuke UranishiDivision of Biomedical Sciences, Research Center for Genomic Medicine, Saitama Medical University, Hidaka, Saitama, Japan.
Aaron B BogutzDepartment of Medical Genetics, Life Sciences Institute, University of British Columbia, Vancouver, British Columbia, Canada.
Sanne M JanssenDepartment of Medical Genetics, Life Sciences Institute, University of British Columbia, Vancouver, British Columbia, Canada.ORCID http://orcid.org/0000-0002-9389-8846
Ayumu SuzukiDivision of Biomedical Sciences, Research Center for Genomic Medicine, Saitama Medical University, Hidaka, Saitama, Japan.
Akihiko OkudaDivision of Biomedical Sciences, Research Center for Genomic Medicine, Saitama Medical University, Hidaka, Saitama, Japan.ORCID http://orcid.org/0000-0002-5298-5564
Haruhiko KosekiLaboratory for Developmental Genetics, RIKEN Center for Integrative Medical Sciences (IMS), Yokohama, Kanagawa, Japan.ORCID http://orcid.org/0000-0001-8424-5854
Matthew C LorinczDepartment of Medical Genetics, Life Sciences Institute, University of British Columbia, Vancouver, British Columbia, Canada. mlorincz@mail.ubc.ca.ORCID http://orcid.org/0000-0003-0885-0467
University of British Columbia · CASaitama Medical University · JPChiba University · JPKyushu University · JPRIKEN Center for Integrative Medical Sciences · JP

Funding

CIHR PJT-153049CIHR PJT-166170
6 · The paper itself

Abstract

Silencing of a subset of germline genes is dependent upon DNA methylation (DNAme) post-implantation. However, these genes are generally hypomethylated in the blastocyst, implicating alternative repressive pathways before implantation. Indeed, in embryonic stem cells (ESCs), an overlapping set of genes, including germline "genome-defence" (GGD) genes, are upregulated following deletion of the H3K9 methyltransferase SETDB1 or subunits of the non-canonical PRC1 complex PRC1.6. Here, we show that in pre-implantation embryos and naïve ESCs (nESCs), hypomethylated promoters of germline genes bound by the PRC1.6 DNA-binding subunits MGA/MAX/E2F6 are enriched for RING1B-dependent H2AK119ub1 and H3K9me3. Accordingly, repression of these genes in nESCs shows a greater dependence on PRC1.6 than DNAme. In contrast, GGD genes are hypermethylated in epiblast-like cells (EpiLCs) and their silencing is dependent upon SETDB1, PRC1.6/RING1B and DNAme, with H3K9me3 and DNAme establishment dependent upon MGA binding. Thus, GGD genes are initially repressed by PRC1.6, with DNAme subsequently engaged in post-implantation embryos.

Indexed as

Gene Expression Regulation, DevelopmentalAnimalsBasic Helix-Loop-Helix Leucine Zipper Transcription FactorsBasic Helix-Loop-Helix ProteinsDNA MethylationE2F6 Transcription FactorEmbryo ImplantationEmbryo, MammalianEpigenesis, GeneticFemaleGene SilencingGenes, ReporterGreen Fluorescent ProteinsHistone-Lysine N-MethyltransferaseHistonesMaleBasic Helix-Loop-Helix Leucine Zipper Transcription FactorsBasic Helix-Loop-Helix ProteinsE2f6 protein, mouseE2F6 Transcription Factorenhanced green fluorescent proteinGreen Fluorescent ProteinsHistone-Lysine N-MethyltransferaseHistonesMax protein, mouseMga protein, mousePolycomb-Group ProteinsPolycomb Repressive Complex 1Protein SubunitsRnf2 protein, mouseSETDB1 protein, mouseUbiquitin-Protein Ligases

Identifiers

PMID34857746
PMCPMC8639735
OpenAlexW3153627057

What Socratic holds

Textmetadata
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 Socratic graph.