Evidence map›Paper›PMID 26952936›Full record

ArticleBiochimica et biophysica acta2016

Epigenetic response to environmental stress: Assembly of BRG1-G9a/GLP-DNMT3 repressive chromatin complex on Myh6 promoter in pathologically stressed hearts.

Pei Han, Wei Li, Jin Yang, Ching Shang, Chiou-Hong Lin, Wei Cheng, Calvin T Hang, Hsiu-Ling Cheng, Chen-Hao Chen, Johnson Wong and 9 more

Open access · greenAbstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Biochimica et biophysica acta, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 44 papers.

0numbers the graph read from it
0cells of the map it votes in
44citing papers in PubMed
4.5field-weighted citation impact, top 5% 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

44 citing papers in PubMed, 68 citations in OpenAlex.

  1. Review
  2. Review
  3. Review
  4. Review
  5. Epigenetic Mechanisms in Heart Diseases.Reviews in cardiovascular medicine · 2025
    Review
  6. Review
  7. Epigenetics in Heart Failure.International journal of molecular sciences · 2024
    Review
  8. Review
  9. Epigenetics in diabetic cardiomyopathy.Clinical epigenetics · 2024
    Review
  10. Article
  11. Review
  12. Review
  13. Review
  14. Review
  15. Article
  16. Review
  17. Review
  18. The Mechanism of Stem Cell Aging.Stem cell reviews and reports · 2022
    Review
  19. Review
  20. Review
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

19 authors at 6 institutions in 1 country.

Pei HanKrannert Institute of Cardiology and Division of Cardiology, Department of Medicine, Indiana University School of Medicine, Indianapolis, IN 46202, USA; Division of Cardiovascular Medicine, Department of Medicine, Stanford University, Stanford, CA 94305, USA.
Wei LiKrannert Institute of Cardiology and Division of Cardiology, Department of Medicine, Indiana University School of Medicine, Indianapolis, IN 46202, USA; Division of Cardiovascular Medicine, Department of Medicine, Stanford University, Stanford, CA 94305, USA.
Jin YangKrannert Institute of Cardiology and Division of Cardiology, Department of Medicine, Indiana University School of Medicine, Indianapolis, IN 46202, USA.
Ching ShangKrannert Institute of Cardiology and Division of Cardiology, Department of Medicine, Indiana University School of Medicine, Indianapolis, IN 46202, USA; Division of Cardiovascular Medicine, Department of Medicine, Stanford University, Stanford, CA 94305, USA.
Chiou-Hong LinDivision of Cardiovascular Medicine, Department of Medicine, Stanford University, Stanford, CA 94305, USA.
Wei ChengKrannert Institute of Cardiology and Division of Cardiology, Department of Medicine, Indiana University School of Medicine, Indianapolis, IN 46202, USA.
Calvin T HangKrannert Institute of Cardiology and Division of Cardiology, Department of Medicine, Indiana University School of Medicine, Indianapolis, IN 46202, USA; Division of Cardiovascular Medicine, Department of Medicine, Stanford University, Stanford, CA 94305, USA.
Hsiu-Ling ChengDivision of Cardiovascular Medicine, Department of Medicine, Stanford University, Stanford, CA 94305, USA.
Chen-Hao ChenDivision of Cardiovascular Medicine, Department of Medicine, Stanford University, Stanford, CA 94305, USA.
Johnson WongDel E. Webb Neuroscience, Aging & Stem Cell Research Center, Sanford/Burnham Medical Research Institute, La Jolla, CA 92037, USA.
Yiqin XiongDivision of Cardiovascular Medicine, Department of Medicine, Stanford University, Stanford, CA 94305, USA.
Mingming ZhaoDivision of Cardiovascular Medicine, Department of Pediatrics, Stanford University, Stanford, CA 94305, USA.
Stavros G DrakosCardiovascular Department and Utah Artificial Heart Program, Intermountain Medical Center, Salt Lake City, UT 84112, USA.
Andrea GhettiAnaBios Corporation, 3030 Bunker Hill St., San Diego, CA 92109, USA.
Dean Y LiCardiovascular Department and Utah Artificial Heart Program, Intermountain Medical Center, Salt Lake City, UT 84112, USA.
Daniel BernsteinDivision of Cardiovascular Medicine, Department of Pediatrics, Stanford University, Stanford, CA 94305, USA.
Huei-Sheng Vincent ChenDel E. Webb Neuroscience, Aging & Stem Cell Research Center, Sanford/Burnham Medical Research Institute, La Jolla, CA 92037, USA.
Thomas QuertermousDivision of Cardiovascular Medicine, Department of Medicine, Stanford University, Stanford, CA 94305, USA.
Ching-Pin ChangKrannert Institute of Cardiology and Division of Cardiology, Department of Medicine, Indiana University School of Medicine, Indianapolis, IN 46202, USA; Krannert Institute of Cardiology and Division of Cardiology, Department of Biochemistry and Molecular Biology, Indiana University School of Medicine, Indianapolis, IN 46202, USA; Krannert Institute of Cardiology and Division of Cardiology, Department of Medical and Molecular Genetics, Indiana University School of Medicine, Indianapolis, IN 46202, USA. Electronic address: changcp@iu.edu.
Stanford University · USCardiovascular Institute of the South · USIndiana University School of MedicineIntermountain Medical Center · USSanford Burnham Prebys Medical Discovery Institute · USAnaBios (United States) · US

Funding

LncRNA mechanism of heart failureR01HL121197 · NHLBI · INDIANA UNIVERSITY INDIANAPOLIS · PI CHANG, CHING-PIN · 2014 to 2022
$3.8M
Chromatin mechanism of molecular motor gene regulationR01HL118087 · NHLBI · INDIANA UNIVERSITY INDIANAPOLIS · PI CHANG, CHING-PIN · 2013 to 2016
$1.5M
NHLBI NIH HHS R01 HL118087NHLBI NIH HHS R01HL118087NHLBI NIH HHS R01 HL121197NHLBI NIH HHS R01HL121197
6 · The paper itself

Abstract

Chromatin structure is determined by nucleosome positioning, histone modifications, and DNA methylation. How chromatin modifications are coordinately altered under pathological conditions remains elusive. Here we describe a stress-activated mechanism of concerted chromatin modification in the heart. In mice, pathological stress activates cardiomyocytes to express Brg1 (nucleosome-remodeling factor), G9a/Glp (histone methyltransferase), and Dnmt3 (DNA methyltransferase). Once activated, Brg1 recruits G9a and then Dnmt3 to sequentially assemble repressive chromatin-marked by H3K9 and CpG methylation-on a key molecular motor gene (Myh6), thereby silencing Myh6 and impairing cardiac contraction. Disruption of Brg1, G9a or Dnmt3 erases repressive chromatin marks and de-represses Myh6, reducing stress-induced cardiac dysfunction. In human hypertrophic hearts, BRG1-G9a/GLP-DNMT3 complex is also activated; its level correlates with H3K9/CpG methylation, Myh6 repression, and cardiomyopathy. Our studies demonstrate a new mechanism of chromatin assembly in stressed hearts and novel therapeutic targets for restoring Myh6 and ventricular function. The stress-induced Brg1-G9a-Dnmt3 interactions and sequence of repressive chromatin assembly on Myh6 illustrates a molecular mechanism by which the heart epigenetically responds to environmental signals. This article is part of a Special Issue entitled: Cardiomyocyte Biology: Integration of Developmental and Environmental Cues in the Heart edited by Marcus Schaub and Hughes Abriel.

Indexed as

Chromatin Assembly and DisassemblyEpigenesis, GeneticPromoter Regions, GeneticStress, PhysiologicalAdaptation, PhysiologicalAnimalsCardiomegalyCardiomyopathiesChromatinCpG IslandsDisease Models, AnimalDNA (Cytosine-5-)-MethyltransferasesDNA HelicasesDNA MethylationDNA Methyltransferase 3AGestational AgeChromatinDNA (Cytosine-5-)-MethyltransferasesDNA HelicasesDNA Methyltransferase 3ADNMT3A protein, humanG9a protein, mouseGLP protein, mouseHistone-Lysine N-MethyltransferaseHistonesMyh6 protein, mouseMyosin Heavy ChainsNuclear ProteinsSmarca4 protein, mouseTranscription FactorsBrg1Cardiac hypertrophyCardiomyopathyChromatin remodelingDNA methylationDnmtG9aGene silencingH3K9me2Heart failureHistone methylationMyosin heavy chain

Identifiers

PMID26952936
PMCPMC7397641
OpenAlexW2290608231

What OpenQuestion holds

Textmetadata
LicenceTDM
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.