Evidence map›Paper›PMID 33847380›Full record

ArticleThe EMBO journal2021

A necessary role of DNMT3A in endurance exercise by suppressing ALDH1L1-mediated oxidative stress.

Sneha Damal Villivalam, Scott M Ebert, Hee Woong Lim, Jinse Kim, Dongjoo You, Byung Chul Jung, Hector H Palacios, Tabitha Tcheau, Christopher M Adams, Sona Kang

Open access · greenAbstract read
In one paragraph

Article in The EMBO journal, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 29 papers.

0numbers the graph read from it
0cells of the map it votes in
29citing papers in PubMed
2.4field-weighted citation impact, top 10% 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

29 citing papers in PubMed, 42 citations in OpenAlex.

  1. Article
  2. Article
  3. Article
  4. Article
  5. Review
  6. Review
  7. Article
  8. SIRT2 and NADAging cell · 2025
    Article
  9. Insulin-Like Growth Factor 2 Reverses Synaptic and Cognitive Deficits in Fetal Growth Restriction Mice.FASEB journal : official publication of the Federation of American Societies for Experimental Biology · 2025
    Article
  10. Article
  11. Review
  12. Article
  13. Review
  14. Review
  15. Article
  16. Article
  17. Article
  18. Article
  19. 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

10 authors at 3 institutions in 1 country.

Sneha Damal VillivalamNutritional Sciences and Toxicology Department, University of California Berkeley, Berkeley, CA, USA.ORCID 0000-0003-4435-3943
Scott M EbertDepartments of Internal Medicine and Molecular Physiology and Biophysics and Fraternal Order of Eagles Diabetes Research Center, University of Iowa, Iowa City, IA, USA.
Hee Woong LimDivision of Biomedical Informatics, Cincinnati Children's Hospital Medical Center, Department of Pediatrics & Biomedical Informatics, University of Cincinnati, Cincinnati, OH, USA.ORCID 0000-0001-8599-1808
Jinse KimNutritional Sciences and Toxicology Department, University of California Berkeley, Berkeley, CA, USA.ORCID 0000-0001-8759-3619
Dongjoo YouNutritional Sciences and Toxicology Department, University of California Berkeley, Berkeley, CA, USA.
Byung Chul JungNutritional Sciences and Toxicology Department, University of California Berkeley, Berkeley, CA, USA.
Hector H PalaciosNutritional Sciences and Toxicology Department, University of California Berkeley, Berkeley, CA, USA.
Tabitha TcheauNutritional Sciences and Toxicology Department, University of California Berkeley, Berkeley, CA, USA.
Christopher M AdamsDepartments of Internal Medicine and Molecular Physiology and Biophysics and Fraternal Order of Eagles Diabetes Research Center, University of Iowa, Iowa City, IA, USA.
Sona KangNutritional Sciences and Toxicology Department, University of California Berkeley, Berkeley, CA, USA.ORCID 0000-0002-9831-677X
University of California, Berkeley · USUniversity of Iowa · USCincinnati Children's Hospital Medical Center · US

Funding

Epigenetic regulation of adipose development and remodelingR01DK116008 · NIDDK · UNIVERSITY OF CALIFORNIA BERKELEY · PI Sona Kang · 2018 to 2026
$3.6M
Novel Signaling Pathways Underlying Skeletal Muscle AtrophyR01AG060637 · NIA · UNIVERSITY OF IOWA · PI ADAMS, CHRISTOPHER M · 2018 to 2022
$2.6M
Molecular pathogenesis of skeletal muscle atrophyR01AR071762 · NIAMS · UNIVERSITY OF IOWA · PI ADAMS, CHRISTOPHER M · 2017 to 2021
$2.4M
BLRD VA I01 BX000976NIAMS NIH HHS R01 AR071762NIA NIH HHS R01 AG060637NIDDK NIH HHS R01 DK116008
6 · The paper itself

Abstract

Exercise can alter the skeletal muscle DNA methylome, yet little is known about the role of the DNA methylation machinery in exercise capacity. Here, we show that DNMT3A expression in oxidative red muscle increases greatly following a bout of endurance exercise. Muscle-specific Dnmt3a knockout mice have reduced tolerance to endurance exercise, accompanied by reduction in oxidative capacity and mitochondrial respiration. Moreover, Dnmt3a-deficient muscle overproduces reactive oxygen species (ROS), the major contributors to muscle dysfunction. Mechanistically, we show that DNMT3A suppresses the Aldh1l1 transcription by binding to its promoter region, altering its epigenetic profile. Forced expression of ALDH1L1 elevates NADPH levels, which results in overproduction of ROS by the action of NADPH oxidase complex, ultimately resulting in mitochondrial defects in myotubes. Thus, inhibition of ALDH1L1 pathway can rescue oxidative stress and mitochondrial dysfunction from Dnmt3a deficiency in myotubes. Finally, we show that in vivo knockdown of Aldh1l1 largely rescues exercise intolerance in Dnmt3a-deficient mice. Together, we establish that DNMT3A in skeletal muscle plays a pivotal role in endurance exercise by controlling intracellular oxidative stress.

Indexed as

AnimalsCell LineDNA (Cytosine-5-)-MethyltransferasesDNA Methyltransferase 3AFormyltetrahydrofolate DehydrogenaseGene Expression ProfilingGene Knockout TechniquesMiceMitochondria, MuscleMuscle, SkeletalOxidative StressOxidoreductases Acting on CH-NH Group DonorsPhysical EnduranceRatsReactive Oxygen SpeciesSequence Analysis, RNADNA (Cytosine-5-)-MethyltransferasesDNA Methyltransferase 3ADnmt3a protein, mouseFormyltetrahydrofolate DehydrogenaseOxidoreductases Acting on CH-NH Group DonorsReactive Oxygen SpeciesDNA methylationexerciseoxidative stress

Identifiers

PMID33847380
PMCPMC8090849
OpenAlexW3155238674

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.