Evidence map›Paper›PMID 23042785›Full record

ArticleHuman molecular genetics2013

Control of epigenetic states by WT1 via regulation of de novo DNA methyltransferase 3A.

Marianna Szemes, Anthony R Dallosso, Zsombor Melegh, Thomas Curry, Yifan Li, Caroline Rivers, James Uney, Ann-Sophie Mägdefrau, Karolin Schwiderski, Ji H Park and 4 more

Open access · bronzeAbstract read
In one paragraph

Article in Human molecular genetics, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 23 papers.

0numbers the graph read from it
0cells of the map it votes in
23citing papers in PubMed
1.5field-weighted citation impact, top 18% 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

23 citing papers in PubMed, 50 citations in OpenAlex.

  1. Article
  2. Article
  3. Article
  4. Review
  5. Article
  6. Article
  7. Article
  8. Article
  9. Article
  10. Epigenetic regulation of renal development.Seminars in cell & developmental biology · 2019
    Review
  11. Review
  12. Article
  13. Review
  14. Article
  15. Article
  16. Article
  17. Article
  18. Review
  19. Article
  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

14 authors at 3 institutions in 2 countries.

Marianna SzemesCancer Epigenetics Laboratory, Cellular and Molecular Medicine, School of Medical Sciences, University of Bristol, Bristol BS8 1TD, UK.
Anthony R Dallosso
Zsombor Melegh
Thomas Curry
Yifan Li
Caroline Rivers
James Uney
Ann-Sophie Mägdefrau
Karolin Schwiderski
Ji H Park
Keith W Brown
Jayasha Shandilya
Stefan G E Roberts
Karim Malik
University of Bristol · GBSouthmead Hospital · GBUniversity at Buffalo, State University of New York · US

Funding

Functional analysis of the WT1-BASP1 transcriptional repressor complexR01GM098609 · NIGMS · STATE UNIVERSITY OF NEW YORK AT BUFFALO · PI MEDLER, KATHRYN, ROBERTS, STEFAN · 2012 to 2015
$1.2M
Biotechnology and Biological Sciences Research Council BB/F022298/1Cancer Research UK 12743Cancer Research UK C20791/A12743NIGMS NIH HHS R01 GM098609
6 · The paper itself

Abstract

Although tumour suppressor gene hypermethylation is a universal feature of cancer cells, little is known about the necessary molecular triggers. Here, we show that Wilms' tumour 1 (WT1), a developmental master regulator that can also act as a tumour suppressor or oncoprotein, transcriptionally regulates the de novo DNA methyltransferase 3A (DNMT3A) and that cellular WT1 levels can influence DNA methylation of gene promoters genome-wide. Specifically, we demonstrate that depletion of WT1 by short-interfering RNAs leads to reduced DNMT3A in Wilms' tumour cells and human embryonal kidney-derived cell lines. Chromatin immunoprecipitation assays demonstrate WT1 recruitment to the DNMT3A promoter region and reporter assays confirm that WT1 directly transactivates DNMT3A expression. Consistent with this regulatory role, immunohistochemical analysis shows co-expression of WT1 and DNMT3A proteins in nuclei of blastemal cells in human fetal kidney and Wilms' tumours. Using genome-wide promoter methylation arrays, we show that human embryonal kidney cells over-expressing WT1 acquire DNA methylation changes at specific gene promoters where DNMT3A recruitment is increased, with hypermethylation being associated with silencing of gene expression. Elevated DNMT3A is also demonstrated at hypermethylated genes in Wilms' tumour cells, including a region of long-range epigenetic silencing. Finally, we show that depletion of WT1 in Wilms' tumour cells can lead to reactivation of gene expression from methylated promoters, such as TGFB2, a key modulator of epithelial-mesenchymal transitions. Collectively, our work defines a new regulatory modality for WT1 involving elicitation of epigenetic alterations which is most likely crucial to its functions in development and disease.

Indexed as

Epigenesis, GeneticGene Expression Regulation, EnzymologicCell LineChromatin ImmunoprecipitationDNA (Cytosine-5-)-MethyltransferasesDNA Methyltransferase 3AGene SilencingHumansPromoter Regions, GeneticTranscription, GeneticWilms TumorWT1 ProteinsDNA (Cytosine-5-)-MethyltransferasesDNA Methyltransferase 3ADNMT3A protein, humanWT1 Proteins

Identifiers

PMID23042785
PMCPMC6296327
OpenAlexW2145588307

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.