Evidence map›Paper›PMID 31074890›Full record

ArticleAlcoholism, clinical and experimental research2019

Global DNA Methylation and Histone Posttranslational Modifications in Human and Nonhuman Primate Brain in Association with Prenatal Alcohol Exposure.

Jessica S Jarmasz, Hannah Stirton, Duaa Basalah, James R Davie, Sterling K Clarren, Susan J Astley, Marc R Del Bigio

Abstract read
In one paragraph

Article in Alcoholism, clinical and experimental research, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 18 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
18citing papers in PubMed, 1 pooled it
–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

18 citing papers in PubMed, 1 synthesis or guideline pooled it.

  1. Pooled it
  2. Article
  3. Review
  4. Article
  5. Review
  6. Review
  7. Article
  8. Review
  9. Article
  10. Review
  11. DNA Methylation in Alcohol Use Disorder.International journal of molecular sciences · 2023
    Review
  12. Fetal alcohol spectrum disorders.Nature reviews. Disease primers · 2023
    Review
  13. Review
  14. Article
  15. Histone Methylation Regulation in Neurodegenerative Disorders.International journal of molecular sciences · 2021
    Review
  16. Article
  17. Article
  18. 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

7 authors.

Jessica S JarmaszDepartment of Pathology, University of Manitoba, Winnipeg, Manitoba, Canada.
Hannah StirtonMax Rady College of Medicine, University of Manitoba, Winnipeg, Manitoba, Canada.
Duaa BasalahDepartment of Pathology, University of Manitoba, Winnipeg, Manitoba, Canada.
James R DavieDepartment of Biochemistry and Medical Genetics, University of Manitoba, Winnipeg, Manitoba, Canada.
Sterling K ClarrenDepartment of Pediatrics, University of Washington School of Medicine, Seattle, Washington, USA.
Susan J AstleyDepartments of Epidemiology/Pediatrics, University of Washington, Seattle, Washington.
Marc R Del BigioDepartment of Pathology, University of Manitoba, Winnipeg, Manitoba, Canada.ORCID 0000-0001-8366-0394

Funding

Canada Israel International Fetal Alcohol ConsortiumCanada Research ChairsCIHR TEC-128094Liquor and Gaming Authority of ManitobaUSPHS AA05616USPHS HD02274USPHS RR00166
6 · The paper itself

Abstract

backgroundBased upon experimental animal studies, the neurodevelopmental abnormalities associated with prenatal alcohol exposure (PNAE)/fetal alcohol spectrum disorder (FASD) have been attributed, at least in part, to epigenetic modifications. However, there are no direct analyses of human brain tissue.

methodsImmunohistochemical detection of global epigenetic markers was performed on temporal lobe samples of autopsied fetuses and infants with documented PNAE. They were compared to age-, sex-, and postmortem delay-matched control cases (18 pairs; 20 to 70.5 weeks postconception). Temporal lobe tissue from a macaque monkey model of PNAE was also studied (5.7 to 6 months of age). We used antibodies targeting 4 DNA cytosine, 4 histone methylation, and 6 histone acetylation modifications and assigned scores based upon the semiquantitatively graded intensity and proportion of positively labeled nuclei in the ventricular and subventricular zones, ependyma, temporal cortex, temporal white matter, dentate gyrus (DG), and CA1 pyramidal layer.

resultsTemporal changes were identified for almost all marks according to the state of maturation in the human brain. In the DG (and 3 other brain regions), a statistically significant increase in H3K9ac was associated with PNAE. Statistically significant decreases were seen among 5mC, H3K4me3, H3K9ac, H3K27ac, H4K12ac, and H4K16ac in select regions. In the macaques, H3K36me3 decreased in the DG, and the ependyma showed decreases in 5fC and H3K36me3.

conclusionsIn human brain, global intranuclear epigenetic modifications are brain region and maturation state-specific. These exploratory results support the general hypothesis that PNAE is associated with a global decrease in DNA methylation, a global decrease in histone methylation, and a global increase in histone acetylation. Although the human and monkey subjects are not directly comparable in terms of brain maturation, considering the rapid temporal changes in global epigenetic modifications during brain development, interspecies comparisons may be extremely difficult.

Indexed as

Maternal ExposureAnimalsBrainCentral Nervous System DepressantsCohort StudiesDNA MethylationEthanolFemaleFetusHistone CodeHumansInfant, NewbornMacaca nemestrinaMalePregnancyPrenatal Exposure Delayed EffectsCentral Nervous System DepressantsEthanolAcetylationEpigeneticsHuman BrainMethylationPrenatal Alcohol

Identifiers

PMID31074890
PMCPMC6593679

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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.