Evidence map›Paper›PMID 27618282›Full record

ArticleDevelopmental cell2016

Stage-Specific Demethylation in Primordial Germ Cells Safeguards against Precocious Differentiation.

Joseph Hargan-Calvopina, Sara Taylor, Helene Cook, Zhongxun Hu, Serena A Lee, Ming-Ren Yen, Yih-Shien Chiang, Pao-Yang Chen, Amander T Clark

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

Article in Developmental cell, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 64 papers.

0numbers the graph read from it
0cells of the map it votes in
64citing papers in PubMed
6.4field-weighted citation impact, top 3% 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

64 citing papers in PubMed, 119 citations in OpenAlex.

  1. Article
  2. Article
  3. Article
  4. In vitro models of the male reproductive system: applications for developmental and reproductive toxicology.Toxicological sciences : an official journal of the Society of Toxicology · 2025
    Review
  5. Article
  6. Review
  7. Article
  8. Review
  9. Article
  10. Article
  11. Review
  12. Review
  13. Review
  14. Article
  15. Review
  16. Epigenetic priming in the male germline.Current opinion in genetics & development · 2024
    Review
  17. Induction of Meiosis from Human Pluripotent Stem Cells.bioRxiv : the preprint server for biology · 2024
    Article
  18. Article
  19. Review
  20. Article

4 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

9 authors at 3 institutions in 2 countries.

Joseph Hargan-CalvopinaDepartment of Molecular Cell and Developmental Biology, University of California, Los Angeles, Los Angeles, CA 90095, USA.
Sara TaylorDepartment of Molecular Cell and Developmental Biology, University of California, Los Angeles, Los Angeles, CA 90095, USA.
Helene CookDepartment of Molecular Cell and Developmental Biology, University of California, Los Angeles, Los Angeles, CA 90095, USA.
Zhongxun HuDepartment of Molecular Cell and Developmental Biology, University of California, Los Angeles, Los Angeles, CA 90095, USA.
Serena A LeeDepartment of Molecular Cell and Developmental Biology, University of California, Los Angeles, Los Angeles, CA 90095, USA.
Ming-Ren YenInstitute of Plant and Microbial Biology, Academia Sinica, Taipei 11529, Taiwan.
Yih-Shien ChiangInstitute of Plant and Microbial Biology, Academia Sinica, Taipei 11529, Taiwan.
Pao-Yang ChenInstitute of Plant and Microbial Biology, Academia Sinica, Taipei 11529, Taiwan.
Amander T ClarkDepartment of Molecular Cell and Developmental Biology, University of California, Los Angeles, Los Angeles, CA 90095, USA; Eli and Edythe Broad Center of Regenerative Medicine and Stem Cell Research, University of California, Los Angeles, Los Angeles, CA 90095, USA; Molecular Biology Institute, University of California, Los Angeles, Los Angeles, CA 90095, USA; Jonsson Comprehensive Cancer Center, University of California, Los Angeles, Los Angeles, CA 90095, USA. Electronic address: clarka@ucla.edu.
University of California, Los Angeles · USInstitute of Plant and Microbial Biology, Academia Sinica · TWBroad Center · US

Funding

Understanding Epigenetic Remodeling in Primordial Germ CellsR01HD058047 · NICHD · UNIVERSITY OF CALIFORNIA LOS ANGELES · PI CLARK, AMANDER · 2009 to 2023
$5.6M
NICHD NIH HHS R01 HD058047
6 · The paper itself

Abstract

Remodeling DNA methylation in mammalian genomes can be global, as seen in preimplantation embryos and primordial germ cells (PGCs), or locus specific, which can regulate neighboring gene expression. In PGCs, global and locus-specific DNA demethylation occur in sequential stages, with an initial global decrease in methylated cytosines (stage I) followed by a Tet methylcytosine dioxygenase (Tet)-dependent decrease in methylated cytosines that act at imprinting control regions (ICRs) and meiotic genes (stage II). The purpose of the two-stage mechanism is unclear. Here we show that Dnmt1 preserves DNA methylation through stage I at ICRs and meiotic gene promoters and is required for the pericentromeric enrichment of 5hmC. We discovered that the functional consequence of abrogating two-stage DNA demethylation in PGCs was precocious germline differentiation leading to hypogonadism and infertility. Therefore, bypassing stage-specific DNA demethylation has significant consequences for progenitor germ cell differentiation and the ability to transmit DNA from parent to offspring.

Indexed as

5-MethylcytosineAnimalsCell DifferentiationDNA (Cytosine-5-)-Methyltransferase 1DNA (Cytosine-5-)-MethyltransferasesDNA MethylationEmbryo, MammalianFemaleGene DeletionGerm CellsMaleMeiosisMice, KnockoutPromoter Regions, GeneticRNA-Binding Proteins5-hydroxymethylcytosine5-MethylcytosineDAZL protein, mouseDNA (Cytosine-5-)-Methyltransferase 1DNA (Cytosine-5-)-MethyltransferasesDnmt1 protein, mouseRNA-Binding Proteins

Identifiers

PMID27618282
PMCPMC5064860
OpenAlexW2520507621

What OpenQuestion holds

Textmetadata
LicenceTDM
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.