Evidence map›Paper›PMID 24947998›Full record

ArticleJournal of the American Heart Association2014

DNA methylation is developmentally regulated for genes essential for cardiogenesis.

Alyssa A Chamberlain, Mingyan Lin, Rolanda L Lister, Alex A Maslov, Yidong Wang, Masako Suzuki, Bingruo Wu, John M Greally, Deyou Zheng, Bin Zhou

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

Article in Journal of the American Heart Association, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 56 papers.

0numbers the graph read from it
0cells of the map it votes in
56citing papers in PubMed
3.0field-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

56 citing papers in PubMed, 86 citations in OpenAlex.

  1. Review
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  10. Human Genetics of Congenital Heart Defects.Advances in experimental medicine and biology · 2024
    Review
  11. Article
  12. Article
  13. Genes · 2023
    Article
  14. Article
  15. Article
  16. Article
  17. Epigenetics in Congenital Heart Disease.Journal of the American Heart Association · 2022
    Review
  18. Article
  19. Article
  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

10 authors at 3 institutions in 2 countries.

Alyssa A ChamberlainDivision of Hematology, Department of Genetics, Albert Einstein College of Medicine of Yeshiva University, Bronx, NY (A.A.C., M.L., A.A.M., Y.W., M.S., B.W., J.M.G., D.Z.).
Mingyan LinDivision of Hematology, Department of Genetics, Albert Einstein College of Medicine of Yeshiva University, Bronx, NY (A.A.C., M.L., A.A.M., Y.W., M.S., B.W., J.M.G., D.Z.).
Rolanda L ListerDivision of Hematology, Department of Obstetrics & Gynecology and Women's Health (Maternal & Fetal Medicine), Albert Einstein College of Medicine of Yeshiva University, Bronx, NY (R.L.L.).
Alex A MaslovDivision of Hematology, Department of Genetics, Albert Einstein College of Medicine of Yeshiva University, Bronx, NY (A.A.C., M.L., A.A.M., Y.W., M.S., B.W., J.M.G., D.Z.).
Yidong WangDivision of Hematology, Department of Genetics, Albert Einstein College of Medicine of Yeshiva University, Bronx, NY (A.A.C., M.L., A.A.M., Y.W., M.S., B.W., J.M.G., D.Z.).
Masako SuzukiDivision of Hematology, Department of Genetics, Albert Einstein College of Medicine of Yeshiva University, Bronx, NY (A.A.C., M.L., A.A.M., Y.W., M.S., B.W., J.M.G., D.Z.).
Bingruo WuDivision of Hematology, Department of Genetics, Albert Einstein College of Medicine of Yeshiva University, Bronx, NY (A.A.C., M.L., A.A.M., Y.W., M.S., B.W., J.M.G., D.Z.).
John M GreallyDivision of Hematology, Department of Medicine, Albert Einstein College of Medicine of Yeshiva University, Bronx, NY (J.M.G.) Division of Hematology, Department of Pediatrics, Albert Einstein College of Medicine of Yeshiva University, Bronx, NY (J.M.G.) Division of Hematology, Department of Genetics, Albert Einstein College of Medicine of Yeshiva University, Bronx, NY (A.A.C., M.L., A.A.M., Y.W., M.S., B.W., J.M.G., D.Z.).
Deyou ZhengDivision of Hematology, Department of Neurology, Albert Einstein College of Medicine of Yeshiva University, Bronx, NY (D.Z.) Division of Hematology, Department of Neuroscience, Albert Einstein College of Medicine of Yeshiva University, Bronx, NY (D.Z.) Division of Hematology, Department of Genetics, Albert Einstein College of Medicine of Yeshiva University, Bronx, NY (A.A.C., M.L., A.A.M., Y.W., M.S., B.W., J.M.G., D.Z.).
Bin ZhouDivision of Cardiology, Departments of Medicine, Pediatrics, and Genetics, and Wilf Family Cardiovascular Research Institute, Albert Einstein College of Medicine of Yeshiva University, Bronx, NY (B.Z.) Department of Cardiology, The First Affiliated Hospital of Nanjing Medical University, Nanjing, China (B.Z.).
Albert Einstein College of Medicine · USYeshiva University · USPediatrics and Genetics · US

Funding

TRAINING PROGRAM IN CELLULAR &MOLEC. BIOLOGY &GENETICST32GM007491 · NIGMS · YESHIVA UNIVERSITY · PI QUERY, CHARLES C · 1985 to 2021
$17.0M
Molecular and Cellular Mechanisms of Calcific Aortic StenosisR01HL111770 · NHLBI · ALBERT EINSTEIN COLLEGE OF MEDICINE, INC · PI ZHOU, BIN · 2012 to 2015
$2.3M
TRANSCRIPTIONAL REGULATION OF ENDOCARDIAL DEVELOPMENTR01HL078881 · NHLBI · VANDERBILT UNIVERSITY · PI ZHOU, BIN · 2006 to 2010
$2.0M
Mouse Model of Human Calcific Aortic Valve StenosisR21HL104444 · NHLBI · ALBERT EINSTEIN COLLEGE OF MEDICINE · PI ZHOU, BIN · 2010 to 2011
$457k
NHLBI NIH HHS HL078881NHLBI NIH HHS HL104444NHLBI NIH HHS HL111770NHLBI NIH HHS R01 HL078881NHLBI NIH HHS R01 HL111770NHLBI NIH HHS R21 HL104444NIGMS NIH HHS GM007491NIGMS NIH HHS T32 GM007491
6 · The paper itself

Abstract

backgroundDNA methylation is a major epigenetic mechanism altering gene expression in development and disease. However, its role in the regulation of gene expression during heart development is incompletely understood. The aim of this study is to reveal DNA methylation in mouse embryonic hearts and its role in regulating gene expression during heart development. METHODS AND

resultsWe performed the genome-wide DNA methylation profiling of mouse embryonic hearts using methyl-sensitive, tiny fragment enrichment/massively parallel sequencing to determine methylation levels at ACGT sites. The results showed that while global methylation of 1.64 million ACGT sites in developing hearts remains stable between embryonic day (E) 11.5 and E14.5, a small fraction (2901) of them exhibit differential methylation. Gene Ontology analysis revealed that these sites are enriched at genes involved in heart development. Quantitative real-time PCR analysis of 350 genes with differential DNA methylation showed that the expression of 181 genes is developmentally regulated, and 79 genes have correlative changes between methylation and expression, including hyaluronan synthase 2 (Has2). Required for heart valve formation, Has2 expression in the developing heart valves is downregulated at E14.5, accompanied with increased DNA methylation in its enhancer. Genetic knockout further showed that the downregulation of Has2 expression is dependent on DNA methyltransferase 3b, which is co-expressed with Has2 in the forming heart valve region, indicating that the DNA methylation change may contribute to the Has2 enhancer's regulating function.

conclusionsDNA methylation is developmentally regulated for genes essential to heart development, and abnormal DNA methylation may contribute to congenital heart disease.

Indexed as

AnimalsDNA (Cytosine-5-)-MethyltransferasesDNA MethylationDNA Methyltransferase 3BGene Expression Regulation, DevelopmentalGenes, DevelopmentalGlucuronosyltransferaseHeartHyaluronan SynthasesMiceMice, Inbred ICRMice, KnockoutOligonucleotide Array Sequence AnalysisReal-Time Polymerase Chain ReactionDNA (Cytosine-5-)-MethyltransferasesDNA Methyltransferase 3BGlucuronosyltransferaseHas2 protein, mouseHyaluronan SynthasesDNA methylationDNA methyltransferase 3bgene expressionheart developmenthyaluronan synthase 2

Identifiers

PMID24947998
PMCPMC4309105
OpenAlexW2108710787

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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.