Evidence map›Paper›PMID 27956497›Full record

ArticleNucleic acids research2017

Non-CpG methylation by DNMT3B facilitates REST binding and gene silencing in developing mouse hearts.

Donghong Zhang, Bingruo Wu, Ping Wang, Yidong Wang, Pengfei Lu, Tamilla Nechiporuk, Thomas Floss, John M Greally, Deyou Zheng, Bin Zhou

Erratum issuedOpen access · goldAbstract read
In one paragraph

Article in Nucleic acids research, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. An erratum has been issued. Cited by 28 papers.

0numbers the graph read from it
0cells of the map it votes in
28citing papers in PubMed
3.0field-weighted citation impact, top 9% 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

28 citing papers in PubMed, 69 citations in OpenAlex.

  1. Article
  2. Review
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  8. Genes · 2023
    Article
  9. Article
  10. Article
  11. Article
  12. Article
  13. Pten Regulates Cardiomyocyte Differentiation by Modulating Non-CG Methylation via Dnmt3.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2021
    Article
  14. Article
  15. Article
  16. Article
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  19. Association of NCell death & disease · 2019
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4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

10 authors at 4 institutions in 3 countries.

Donghong ZhangDepartments of Genetics, Pediatrics, and Medicine (Cardiology), Wilf Cardiovascular Research Institute, Albert Einstein College of Medicine, Bronx, NY 10461, USA.
Bingruo WuDepartments of Genetics, Pediatrics, and Medicine (Cardiology), Wilf Cardiovascular Research Institute, Albert Einstein College of Medicine, Bronx, NY 10461, USA.
Ping WangDepartment of Neurology, Albert Einstein College of Medicine, Bronx, NY 10461, USA.
Yidong WangDepartments of Genetics, Pediatrics, and Medicine (Cardiology), Wilf Cardiovascular Research Institute, Albert Einstein College of Medicine, Bronx, NY 10461, USA.
Pengfei LuDepartments of Genetics, Pediatrics, and Medicine (Cardiology), Wilf Cardiovascular Research Institute, Albert Einstein College of Medicine, Bronx, NY 10461, USA.
Tamilla NechiporukVollum Institute, Oregon Health & Science University, Portland, OR 97239, USA.
Thomas FlossGerman Research Center for Environmental Health, Neuherberg, Germany.
John M GreallyDepartments of Genetics, Medicine (Hematology), and Pediatrics, Albert Einstein College of Medicine, Bronx, NY 10461, USA.
Deyou ZhengDepartments of Genetics, Neurology, and Neuroscience, Albert Einstein College of Medicine, Bronx, NY 10461, USA.
Bin ZhouDepartments of Genetics, Pediatrics, and Medicine (Cardiology), Wilf Cardiovascular Research Institute, Albert Einstein College of Medicine, Bronx, NY 10461, USA.
Albert Einstein College of Medicine · USHelmholtz Zentrum München · DEJiangsu Province Hospital · CNVollum Institute · US

Funding

Translational Research CoreP30DK020541 · NIDDK · ALBERT EINSTEIN COLLEGE OF MEDICINE, INC · PI STREAMSON C CHUA · 2015 to 2026
$27.7M
Molecular and Cellular Mechanisms in Coronary Artery Development and AnomaliesR01HL133120 · NHLBI · UNIVERSITY OF CHICAGO · PI BIN ZHOU · 2016 to 2026
$4.6M
NHLBI NIH HHS R01 HL133120NIDDK NIH HHS P30 DK020541
6 · The paper itself

Abstract

The dynamic interaction of DNA methylation and transcription factor binding in regulating spatiotemporal gene expression is essential for embryogenesis, but the underlying mechanisms remain understudied. In this study, using mouse models and integration of in vitro and in vivo genetic and epigenetic analyses, we show that the binding of REST (repressor element 1 (RE1) silencing transcription factor; also known as NRSF) to its cognate RE1 sequences is temporally regulated by non-CpG methylation. This process is dependent on DNA methyltransferase 3B (DNMT3B) and leads to suppression of adult cardiac genes in developing hearts. We demonstrate that DNMT3B preferentially mediates non-CpG methylation of REST-targeted genes in the developing heart. Downregulation of DNMT3B results in decreased non-CpG methylation of RE1 sequences, reduced REST occupancy, and consequently release of the transcription suppression during later cardiac development. Together, these findings reveal a critical gene silencing mechanism in developing mammalian hearts that is regulated by the dynamic interaction of DNMT3B-mediated non-CpG methylation and REST binding.

Indexed as

Gene Expression Regulation, DevelopmentalGene SilencingAnimalsBinding SitesCells, CulturedCpG IslandsDNA (Cytosine-5-)-MethyltransferasesDNA MethylationDNA Methyltransferase 3BHeartHyperpolarization-Activated Cyclic Nucleotide-Gated ChannelsMiceMice, Inbred C57BLMyocardiumPotassium ChannelsProtein BindingDNA (Cytosine-5-)-MethyltransferasesDNA Methyltransferase 3BHcn2 protein, mouseHyperpolarization-Activated Cyclic Nucleotide-Gated ChannelsPotassium ChannelsRE1-Silencing Transcription FactorRepressor Proteins

Identifiers

PMID27956497
PMCPMC5389556
OpenAlexW2605004805

What OpenQuestion holds

Textmetadata
LicenceCC BY-NC
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.