Evidence map›Paper›PMID 27381023›Full record

ArticleGenome biology2016

Enhancers reside in a unique epigenetic environment during early zebrafish development.

Lucas J T Kaaij, Michal Mokry, Meng Zhou, Michael Musheev, Geert Geeven, Adrien S J Melquiond, António M de Jesus Domingues, Wouter de Laat, Christof Niehrs, Andrew D Smith and 1 more

Abstract read
In one paragraph

Article in Genome biology, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 27 papers.

0numbers the graph read from it
0cells of the map it votes in
27citing 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

27 citing papers in PubMed.

  1. Article
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  8. Upregulation of FAM50A promotes cancer development.Medical oncology (Northwood, London, England) · 2023
    Article
  9. Review
  10. Article
  11. Article
  12. Article
  13. Article
  14. Article
  15. Exploiting regulatory heterogeneity to systematically identify enhancers with high accuracy.Proceedings of the National Academy of Sciences of the United States of America · 2019
    Article
  16. Article
  17. Article
  18. Review
  19. Bloody Zebrafish: Novel Methods in Normal and Malignant Hematopoiesis.Frontiers in cell and developmental biology · 2018
    Article
  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

11 authors.

Lucas J T KaaijInstitute of Molecular Biology (IMB), Ackermannweg 4, D-55128, Mainz, Germany.
Michal MokryDepartment of Pediatric Gastroenterology, Wilhelmina Children's Hospital, University Medical Centre Utrecht, 3508 AB, Utrecht, The Netherlands.
Meng ZhouMolecular and Computational Biology, University of Southern California, Los Angeles, CA, 90089, USA.
Michael MusheevInstitute of Molecular Biology (IMB), Ackermannweg 4, D-55128, Mainz, Germany.
Geert GeevenHubrecht Institute-KNAW & University Medical Centre Utrecht, Uppsalalaan 8, 3584 CT, Utrecht, The Netherlands.
Adrien S J MelquiondHubrecht Institute-KNAW & University Medical Centre Utrecht, Uppsalalaan 8, 3584 CT, Utrecht, The Netherlands.
António M de Jesus DominguesInstitute of Molecular Biology (IMB), Ackermannweg 4, D-55128, Mainz, Germany.
Wouter de LaatHubrecht Institute-KNAW & University Medical Centre Utrecht, Uppsalalaan 8, 3584 CT, Utrecht, The Netherlands.
Christof NiehrsInstitute of Molecular Biology (IMB), Ackermannweg 4, D-55128, Mainz, Germany.
Andrew D SmithMolecular and Computational Biology, University of Southern California, Los Angeles, CA, 90089, USA.
René F KettingInstitute of Molecular Biology (IMB), Ackermannweg 4, D-55128, Mainz, Germany. r.ketting@imb.de.

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

backgroundEnhancers, not promoters, are the most dynamic in their DNA methylation status throughout development and differentiation. Generally speaking, enhancers that are primed to or actually drive gene expression are characterized by relatively low levels of DNA methylation (hypo-methylation), while inactive enhancers display hyper-methylation of the underlying DNA. The direct functional significance of the DNA methylation state of enhancers is, however, unclear for most loci.

resultsIn contrast to conventional epigenetic interactions at enhancers, we find that DNA methylation status and enhancer activity during early zebrafish development display very unusual correlation characteristics: hypo-methylation is a unique feature of primed enhancers whereas active enhancers are generally hyper-methylated. The hypo-methylated enhancers that we identify (hypo-enhancers) are enriched close to important transcription factors that act later in development. Interestingly, hypo-enhancers are de-methylated shortly before the midblastula transition and reside in a unique epigenetic environment. Finally, we demonstrate that hypo-enhancers do become active at later developmental stages and that they are physically associated with the transcriptional start site of target genes, irrespective of target gene activity.

conclusionsWe demonstrate that early development in zebrafish embodies a time window characterized by non-canonical DNA methylation-enhancer relationships, including global DNA hypo-methylation of inactive enhancers and DNA hyper-methylation of active enhancers.

Indexed as

Enhancer Elements, GeneticEpigenesis, GeneticAnimalsCell DifferentiationDNA MethylationEmbryonic DevelopmentGene Expression Regulation, DevelopmentalTranscription Initiation SiteZebrafish4CDNA methylationEnhancersPrimingZebrafish development

Identifiers

PMID27381023
PMCPMC4934011

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LicenceCC BY
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Registered trials

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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.