Evidence map›Paper›PMID 23585276›Full record

ArticleNucleic acids research2013

Induced DNA demethylation can reshape chromatin topology at the IGF2-H19 locus.

Yoko Ito, Raffaella Nativio, Adele Murrell

Open access · goldAbstract read
In one paragraph

Article in Nucleic acids research, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 16 papers.

0numbers the graph read from it
0cells of the map it votes in
16citing papers in PubMed
1.9field-weighted citation impact, top 14% 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

16 citing papers in PubMed, 39 citations in OpenAlex.

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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

3 authors at 2 institutions in 2 countries.

Yoko ItoDepartment of Oncology, University of Cambridge, CRUK Cambridge Institute, Robinson Way, Cambridge CB2 0RE, UK.
Raffaella Nativio
Adele Murrell
Philadelphia University · USUniversity of Cambridge · GB

Funding

Cancer Research UK
6 · The paper itself

Abstract

Choriocarcinomas are embryonal tumours with loss of imprinting and hypermethylation at the insulin-like growth factor 2 (IGF2)-H19 locus. The DNA methyltransferase inhibitor, 5-Aza-2'deoxycytidine (5-AzaCdR) is an approved epigenetic cancer therapy. However, it is not known to what extent 5-AzaCdR influences other epigenetic marks. In this study, we set out to determine whether 5-AzaCdR treatment can reprogram the epigenomic organization of the IGF2-H19 locus in a choriocarcinoma cancer cell line (JEG3). We found that localized DNA demethylation at the H19 imprinting control region (ICR) induced by 5-AzaCdR, reduced IGF2, increased H19 expression, increased CTCF and cohesin recruitment and changed histone modifications. Furthermore chromatin accessibility was increased locus-wide and chromatin looping topography was altered such that a CTCF site downstream of the H19 enhancers switched its association with the CTCF site upstream of the IGF2 promoters to associate with the ICR. We identified a stable chromatin looping domain, which forms independently of DNA methylation. This domain contains the IGF2 gene and is marked by a histone H3 lysine 27 trimethylation block between CTCF site upstream of the IGF2 promoters and the Centrally Conserved Domain upstream of the ICR. Together, these data provide new insights into the responsiveness of chromatin topography to DNA methylation changes.

Indexed as

DNA MethylationGenomic ImprintingAzacitidineCCCTC-Binding FactorCell Cycle ProteinsCell Line, TumorChromatinChromosomal Proteins, Non-HistoneCohesinsDecitabineDown-RegulationEnhancer Elements, GeneticEnzyme InhibitorsGene ExpressionGenetic LociHistonesAzacitidineCCCTC-Binding FactorCell Cycle ProteinsChromatinChromosomal Proteins, Non-HistoneCohesinsCTCF protein, humanDecitabineEnzyme InhibitorsH19 long non-coding RNAHistonesIGF2 protein, humanInsulin-Like Growth Factor IIlysin, gastropodaMucoproteinsNeoplasm ProteinsNucleosomesPolycomb Repressive Complex 2Repressor ProteinsRNA, Long NoncodingSUZ12 protein, humanTranscription Factors

Identifiers

PMID23585276
PMCPMC3664821
OpenAlexW2070191145

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.