Evidence map›Paper›PMID 19946145›Full record

ArticleThe Journal of biological chemistry2010

Dnmt3 and G9a cooperate for tissue-specific development in zebrafish.

Kunal Rai, Itrat F Jafri, Stephanie Chidester, Smitha R James, Adam R Karpf, Bradley R Cairns, David A Jones

Open access · hybridAbstract read
In one paragraph

Article in The Journal of biological chemistry, 2010. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 77 papers.

0numbers the graph read from it
0cells of the map it votes in
77citing papers in PubMed
3.2field-weighted citation impact, top 8% 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

77 citing papers in PubMed, 122 citations in OpenAlex.

  1. Global epigenetic immunohistochemical markers reveal developmental connections of distinct cell types during fetal development.Graefe's archive for clinical and experimental ophthalmology = Albrecht von Graefes Archiv fur klinische und experimentelle Ophthalmologie · 2026
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  3. Skeletal Muscle Aging: Lessons From Teleosts.The journals of gerontology. Series A, Biological sciences and medical sciences · 2025
    Review
  4. Article
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  9. Review
  10. Epigenetic Switches in Retinal Homeostasis and Target for Drug Development.International journal of molecular sciences · 2024
    Review
  11. Review
  12. Review
  13. Article
  14. Article
  15. Epigenetic regulation of retinal development.Epigenetics & chromatin · 2021
    Review
  16. Article
  17. Article
  18. Article
  19. Article
  20. Review

17 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

7 authors at 4 institutions in 1 country.

Kunal RaiFrom the Departments of Oncological Sciences, University of Utah, Salt Lake City, Utah 84112; Departments of Huntsman Cancer Institute, University of Utah, Salt Lake City, Utah 84112 and; Departments of Howard Hughes Medical Institute, University of Utah, Salt Lake City, Utah 84112.
Itrat F JafriFrom the Departments of Oncological Sciences, University of Utah, Salt Lake City, Utah 84112; Departments of Huntsman Cancer Institute, University of Utah, Salt Lake City, Utah 84112 and; Departments of Howard Hughes Medical Institute, University of Utah, Salt Lake City, Utah 84112.
Stephanie ChidesterDepartments of Huntsman Cancer Institute, University of Utah, Salt Lake City, Utah 84112 and.
Smitha R Jamesthe Department of Pharmacology and Therapeutics, Roswell Park Cancer Institute, Buffalo, New York 14263.
Adam R Karpfthe Department of Pharmacology and Therapeutics, Roswell Park Cancer Institute, Buffalo, New York 14263.
Bradley R CairnsFrom the Departments of Oncological Sciences, University of Utah, Salt Lake City, Utah 84112; Departments of Huntsman Cancer Institute, University of Utah, Salt Lake City, Utah 84112 and; Departments of Howard Hughes Medical Institute, University of Utah, Salt Lake City, Utah 84112. Electronic address: brad.cairns@hci.utah.edu.
David A JonesFrom the Departments of Oncological Sciences, University of Utah, Salt Lake City, Utah 84112; Departments of Huntsman Cancer Institute, University of Utah, Salt Lake City, Utah 84112 and; Departments of Medicinal Chemistry, University of Utah, Salt Lake City, Utah 84112. Electronic address: david.jones@hci.utah.edu.
University of Utah · USRoswell Park Comprehensive Cancer Center · USHoward Hughes Medical Institute · USHuntsman Cancer Institute · US

Funding

UTAH REGIONAL CANCER CENTERP30CA042014 · NCI · UTAH STATE HIGHER EDUCATION SYSTEM--UNIVERSITY OF UTAH · PI Jared P Rutter · 1986 to 2026
$72.6M
APC and Retinoids in Zebrafish Enterocyte DevelopmentR01CA116468 · NCI · UNIVERSITY OF UTAH · PI JONES, DAVID A · 2005 to 2020
$4.2M
A Center for Zebrafish Chromatin and EpigeneticsR01HD058506 · NICHD · UNIVERSITY OF UTAH · PI CAIRNS, BRADLEY R., JONES, DAVID A · 2008 to 2012
$1.6M
Epigenetic regulation of cancer/germ-line antigen gene expressionR01CA116674 · NCI · UNIVERSITY OF NEBRASKA MEDICAL CENTER · PI KARPF, ADAM R. · 2006 to 2010
$1.4M
Howard Hughes Medical InstituteNCI NIH HHS CA042014NCI NIH HHS P30 CA042014NCI NIH HHS R01 CA116468NCI NIH HHS R01CA116468NCI NIH HHS R01 CA116674NCI NIH HHS R01 CA11674NICHD NIH HHS R01 HD058506
6 · The paper itself

Abstract

Although DNA methylation is critical for proper embryonic and tissue-specific development, how different DNA methyltransferases affect tissue-specific development and their targets remains unknown. We address this issue in zebrafish through antisense-based morpholino knockdown of Dnmt3 and Dnmt1. Our data reveal that Dnmt3 is required for proper neurogenesis, and its absence results in profound defects in brain and retina. Interestingly, other organs such as intestine remain unaffected suggesting tissue-specific requirements of Dnmt3. Further, comparison of Dnmt1 knockdown phenotypes with those of Dnmt3 suggested that these two families have distinct functions. Consistent with this idea, Dnmt1 failed to complement Dnmt3 deficiency, and Dnmt3 failed to complement Dnmt1 deficiency. Downstream of Dnmt3 we identify a neurogenesis regulator, lef1, as a Dnmt3-specific target gene that is demethylated and up-regulated in dnmt3 morphants. Knockdown of lef1 rescued neurogenesis defects resulting from Dnmt3 absence. Mechanistically, we show cooperation between Dnmt3 and an H3K9 methyltransferase G9a in regulating lef1. Further, like Dnmt1-Suv39h1 cooperativity, Dnmt3 and G9a seemed to function together for tissue-specific development. G9a knockdown, but not Suv39h1 loss, phenocopied dnmt3 morphants and G9a overexpression provided a striking rescue of dnmt3 morphant phenotypes, whereas Suv39h1 overexpression failed, supporting the notion of specific DNMT-histone methyltransferase networks. Consistent with this model, H3K9me3 levels on the lef1 promoter were reduced in both dnmt3 and g9a morphants, and its knockdown rescued neurogenesis defects in g9a morphants. We propose a model wherein specific DNMT-histone methyltransferase networks are utilized to silence critical regulators of cell fate in a tissue-specific manner.

Indexed as

AnimalsBrainChromatin ImmunoprecipitationDNA (Cytosine-5-)-Methyltransferase 1DNA (Cytosine-5-)-MethyltransferasesEmbryo, NonmammalianGene Expression ProfilingGene Expression Regulation, EnzymologicGene Knockdown TechniquesHistone-Lysine N-MethyltransferaseIn Situ HybridizationModels, BiologicalNeurogenesisRetinaReverse Transcriptase Polymerase Chain ReactionTranscription FactorsDNA (Cytosine-5-)-Methyltransferase 1DNA (Cytosine-5-)-MethyltransferasesDnmt1 protein, zebrafishHistone-Lysine N-MethyltransferaseLEF1 protein, zebrafishTranscription FactorsZebrafish Proteins

Identifiers

PMID19946145
PMCPMC2823551
OpenAlexW2038253485

What OpenQuestion holds

Textmetadata
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.