Evidence map›Paper›PMID 23449636›Full record

ArticleBlood2013

A mechanistic role for DNA methylation in endothelial cell (EC)-enriched gene expression: relationship with DNA replication timing.

Apurva V Shirodkar, Rosanne St Bernard, Anna Gavryushova, Anna Kop, Britta J Knight, Matthew Shu-Ching Yan, Hon-Sum Jeffrey Man, Maneesh Sud, Robert P Hebbel, Peter Oettgen and 2 more

Open access · hybridAbstract readComparative Study
In one paragraph

Article in Blood, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 35 papers.

0numbers the graph read from it
0cells of the map it votes in
35citing papers in PubMed
3.1field-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

35 citing papers in PubMed, 69 citations in OpenAlex.

  1. Article
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  5. Coronary artery disease and cancer: a significant resemblance.Medical oncology (Northwood, London, England) · 2022
    Review
  6. Article
  7. Review
  8. Review
  9. Review
  10. Review
  11. Cell-specific epigenetic changes in atherosclerosis.Clinical science (London, England : 1979) · 2021
    Review
  12. Article
  13. Article
  14. Article
  15. Review
  16. Article
  17. Article
  18. Article
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  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

12 authors at 4 institutions in 2 countries.

Apurva V ShirodkarDepartment of Medical Biophysics, University of Toronto, Toronto, ON, Canada.
Rosanne St Bernard
Anna Gavryushova
Anna Kop
Britta J Knight
Matthew Shu-Ching Yan
Hon-Sum Jeffrey Man
Maneesh Sud
Robert P Hebbel
Peter Oettgen
William C Aird
Philip A Marsden
University of Toronto · CABeth Israel Deaconess Medical Center · USSt. Michael's Hospital · CAUniversity of Minnesota Medical Center · US

Funding

VASCULAR TOPOGRAPHY OF CD39/NTPDASESP01HL076540 · NHLBI · BETH ISRAEL DEACONESS MEDICAL CENTER · PI AIRD, WILLIAM C · 2004 to 2014
$20.3M
VASCULAR PATHOBIOLOGY OF SICKLE CELL DISEASEP01HL055552 · NHLBI · UNIVERSITY OF MINNESOTA TWIN CITIES · PI HEBBEL, ROBERT P · 1995 to 2011
$17.3M
CIHR MOP79475NHLBI NIH HHS P01 HL055552NHLBI NIH HHS P01 HL076540NHLBI NIH HHS P01 HL076540-06A1
6 · The paper itself

Abstract

Proximal promoter DNA methylation has been shown to be important for regulating gene expression. However, its relative contribution to the cell-specific expression of endothelial cell (EC)-enriched genes has not been defined. We used methyl-DNA immunoprecipitation and bisulfite conversion to analyze the DNA methylation profile of EC-enriched genes in ECs vs nonexpressing cell types, both in vitro and in vivo. We show that prototypic EC-enriched genes exhibit functional differential patterns of DNA methylation in proximal promoter regions of most (eg, CD31, von Willebrand factor [vWF], VE-cadherin, and intercellular adhesion molecule-2), but not all (eg, VEGFR-1 and VEGFR-2), EC-enriched genes. Comparable findings were evident in cultured ECs, human blood origin ECs, and murine aortic ECs. Promoter-reporter episomal transfection assays for endothelial nitric oxide synthase, VE-cadherin, and vWF indicated functional promoter activity in cell types where the native gene was not active. Inhibition of DNA methyltransferase activity indicated important functional relevance. Importantly, profiling DNA replication timing patterns indicated that EC-enriched gene promoters with differentially methylated regions replicate early in S-phase in both expressing and nonexpressing cell types. Collectively, these studies highlight the functional importance of promoter DNA methylation in controlling vascular EC gene expression.

Indexed as

DNA MethylationDNA Replication TimingGene Expression RegulationAnimalsAntigens, CDAortaCadherin 5CadherinsCattleCell Adhesion MoleculesCells, CulturedChromatin ImmunoprecipitationDermisEndothelium, VascularHepatocytesHumansAntigens, CDCadherin 5CadherinsCell Adhesion MoleculesNitric Oxide Synthase Type IIIVascular Endothelial Growth Factor Receptor-1Vascular Endothelial Growth Factor Receptor-2von Willebrand Factor

Identifiers

PMID23449636
PMCPMC3637020
OpenAlexW1965824800

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.