Evidence map›Paper›PMID 29618782›Full record

ArticleScientific reports2018

ETV2-TET1/TET2 Complexes Induce Endothelial Cell-Specific Robo4 Expression via Promoter Demethylation.

Toru Tanaka, Kohei Izawa, Yusuke Maniwa, Maki Okamura, Atsumasa Okada, Tomoko Yamaguchi, Keisuke Shirakura, Naoki Maekawa, Hayato Matsui, Kenji Ishimoto and 7 more

Open access · goldAbstract read
In one paragraph

Article in Scientific reports, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 18 papers.

0numbers the graph read from it
0cells of the map it votes in
18citing papers in PubMed
1.3field-weighted citation impact, top 20% 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

18 citing papers in PubMed, 29 citations in OpenAlex.

  1. Article
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  6. Transcription factors regulating vasculogenesis and angiogenesis.Developmental dynamics : an official publication of the American Association of Anatomists · 2024
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  7. Article
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  10. Endothelial Cell Differentiation and Hemogenic Specification.Cold Spring Harbor perspectives in medicine · 2022
    Review
  11. Article
  12. Article
  13. Review
  14. Review
  15. Review
  16. Review
  17. Review
  18. 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

17 authors at 5 institutions in 2 countries.

Toru TanakaGraduate School of Pharmaceutical Sciences, Osaka University, Suita City, Osaka, 565-0871, Japan.ORCID 0000-0003-0180-2067
Kohei IzawaGraduate School of Pharmaceutical Sciences, Osaka University, Suita City, Osaka, 565-0871, Japan.
Yusuke ManiwaGraduate School of Pharmaceutical Sciences, Osaka University, Suita City, Osaka, 565-0871, Japan.
Maki OkamuraGraduate School of Pharmaceutical Sciences, Osaka University, Suita City, Osaka, 565-0871, Japan.
Atsumasa OkadaLaboratory of Stem Cell Regulation, National Institutes of Biomedical Innovation, Health and Nutrition, Ibaraki City, Osaka, 567-0085, Japan.
Tomoko YamaguchiLaboratory of Stem Cell Regulation, National Institutes of Biomedical Innovation, Health and Nutrition, Ibaraki City, Osaka, 567-0085, Japan.
Keisuke ShirakuraGraduate School of Pharmaceutical Sciences, Osaka University, Suita City, Osaka, 565-0871, Japan.
Naoki MaekawaGraduate School of Pharmaceutical Sciences, Osaka University, Suita City, Osaka, 565-0871, Japan.
Hayato MatsuiGraduate School of Pharmaceutical Sciences, Osaka University, Suita City, Osaka, 565-0871, Japan.
Kenji IshimotoGraduate School of Pharmaceutical Sciences, Osaka University, Suita City, Osaka, 565-0871, Japan.
Nobumasa HinoGraduate School of Pharmaceutical Sciences, Osaka University, Suita City, Osaka, 565-0871, Japan.
Osamu NakagawaDepartment of Molecular Physiology, National Cerebral and Cardiovascular Center Research Institute, Suita City, Osaka, 565-8565, Japan.
William C AirdCenter for Vascular Biology Research and Division of Molecular and Vascular Medicine, Beth Israel Deaconess Medical Center, Boston, MA, 02215, USA.
Hiroyuki MizuguchiGraduate School of Pharmaceutical Sciences, Osaka University, Suita City, Osaka, 565-0871, Japan.
Kenji KawabataLaboratory of Stem Cell Regulation, National Institutes of Biomedical Innovation, Health and Nutrition, Ibaraki City, Osaka, 567-0085, Japan.
Takefumi DoiGraduate School of Pharmaceutical Sciences, Osaka University, Suita City, Osaka, 565-0871, Japan.
Yoshiaki OkadaGraduate School of Pharmaceutical Sciences, Osaka University, Suita City, Osaka, 565-0871, Japan. okadabos@phs.osaka-u.ac.jp.
The University of Osaka · JPNational Institute of Biomedical Innovation, Health and Nutrition · JPBeth Israel Deaconess Medical Center · USNational Cerebral and Cardiovascular Center · JPOsaka University of Pharmaceutical Sciences · JP

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

Although transcription factors regulating endothelial cell (EC)-specific gene expression have been identified, it is not known how those factors induce EC-specificity. We previously reported that DNA hypomethylation of the proximal promoter elicits EC-specific expression of Roundabout4 (Robo4). However, the mechanisms establishing EC-specific hypomethylation of the Robo4 promoter remain unknown. In this study, we demonstrated that the hypermethylated Robo4 proximal promoter is demethylated as human iPS cells differentiate into endothelial cells. Reporter assays demonstrated that ETV2, an ETS family transcription factor, bound to ETS motifs in the proximal promoter and activated Robo4 expression. Immunoprecipitation demonstrated direct interaction between ETV2 and methylcytosine-converting enzymes TET1 and TET2. Adenoviral expression of ETV2-TET1/TET2 complexes demethylated the Robo4 promoter and induced Robo4 expression in non-ECs. In summary, we propose a novel regulatory model of EC-specific gene expression via promoter demethylation induced by ETV2-TET1/TET2 complexes during endothelial differentiation.

Indexed as

DemethylationPromoter Regions, GeneticCells, CulturedDioxygenasesDNA-Binding ProteinsDNA MethylationEndothelium, VascularGene Expression RegulationHumansInduced Pluripotent Stem CellsMixed Function OxygenasesProto-Oncogene ProteinsReceptors, Cell SurfaceRoundabout ProteinsTranscription FactorsDioxygenasesDNA-Binding ProteinsETV2 protein, humanMixed Function OxygenasesProto-Oncogene ProteinsReceptors, Cell SurfaceROBO4 protein, humanRoundabout ProteinsTET1 protein, humanTET2 protein, humanTranscription Factors

Identifiers

PMID29618782
PMCPMC5884809
OpenAlexW2795424754

What OpenQuestion holds

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LicenceCC BY
Read underepoch 390

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.