Evidence map›Paper›PMID 24834974›Full record

ArticleDiabetes2014

Increased DNA methyltransferase 3b (Dnmt3b)-mediated CpG island methylation stimulated by oxidative stress inhibits expression of a gene required for neural tube and neural crest development in diabetic pregnancy.

Dan Wei, Mary R Loeken

Open access · bronzeAbstract read
In one paragraph

Article in Diabetes, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 34 papers.

0numbers the graph read from it
0cells of the map it votes in
34citing papers in PubMed
3.3field-weighted citation impact, top 7% 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

34 citing papers in PubMed, 72 citations in OpenAlex.

  1. Trial
  2. Article
  3. The silent threat: PMArchives of toxicology · 2026
    Review
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  7. Article
  8. Article
  9. Article
  10. The interplay of inflammation, exosomes and CaCardiovascular diabetology · 2023
    Review
  11. Article
  12. Review
  13. Article
  14. Article
  15. Review
  16. Review
  17. Review
  18. Review
  19. Aberrant DNA methylation as a diagnostic biomarker of diabetic embryopathy.Genetics in medicine : official journal of the American College of Medical Genetics · 2019
    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

2 authors at 2 institutions in 1 country.

Dan WeiSection on Islet Cell and Regenerative Biology, Joslin Diabetes Center, and Department of Medicine, Harvard Medical School, Boston, MA.
Mary R LoekenSection on Islet Cell and Regenerative Biology, Joslin Diabetes Center, and Department of Medicine, Harvard Medical School, Boston, MA mary.loeken@joslin.harvard.edu.
Harvard University · USJoslin Diabetes Center · US

Funding

SPECIAL ASSAY COREP30DK036836 · NIDDK · JOSLIN DIABETES CENTER · PI JEAN E. SCHAFFER · 1986 to 2026
$50.5M
MOLECULAR REGULATION: EMBYROGENESIS BY METABOLIC STRESSR01DK058300 · NIDDK · JOSLIN DIABETES CENTER · PI LOEKEN, MARY R · 2000 to 2014
$4.3M
NIDDK NIH HHS P01DK036836NIDDK NIH HHS P30 DK036836NIDDK NIH HHS R01 DK058300NIDDK NIH HHS R01DK058300
6 · The paper itself

Abstract

Previous studies have shown that diabetic embryopathy results from impaired expression of genes that are required for formation of embryonic structures. We have focused on Pax3, a gene that is expressed in embryonic neuroepithelium and is required for neural tube closure. Pax3 expression is inhibited in embryos of diabetic mice due to hyperglycemia-induced oxidative stress. DNA methylation silences developmentally expressed genes before differentiation. We hypothesized that hypomethylation of Pax3 upon neuroepithelial differentiation may be inhibited by hyperglycemia-induced oxidative stress. We tested this using embryos of pregnant hyperglycemic mice and mouse embryonic stem cells (ESC). Methylation of a Pax3 CpG island decreased upon neurulation of embryos and formation of neuronal precursors from ESC. In ESC, this was inhibited by oxidative stress. Use of short hairpin RNA in ESC demonstrated that DNA methyltransferase 3b (Dnmt3b) was responsible for methylation and silencing of Pax3 before differentiation and by oxidative stress. Although expression of Dnmt3b was not affected by oxidative stress, DNA methyltransferase activity was increased. These results indicate that hyperglycemia-induced oxidative stress stimulates Dnmt3b activity, thereby inhibiting chromatin modifications necessary for induction of Pax3 expression during neurulation and thus providing a molecular mechanism for defects caused by Pax3 insufficiency in diabetic pregnancy.

Indexed as

AnimalsCpG IslandsDNA (Cytosine-5-)-MethyltransferasesDNA MethylationDNA Methyltransferase 3BFemaleGene ExpressionHyperglycemiaMiceMice, Inbred ICRNeural CrestNeural TubeOxidative StressPaired Box Transcription FactorsPAX3 Transcription FactorPregnancyDNA (Cytosine-5-)-MethyltransferasesDNA Methyltransferase 3BPaired Box Transcription FactorsPax3 protein, mousePAX3 Transcription Factor

Identifiers

PMID24834974
PMCPMC4171658
OpenAlexW2159027006

What OpenQuestion holds

Textmetadata
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.