Evidence map›Paper›PMID 27593931›Full record

ArticleOncogene2017

Methyl-CpG-binding protein MBD2 plays a key role in maintenance and spread of DNA methylation at CpG islands and shores in cancer.

C Stirzaker, J Z Song, W Ng, Q Du, N J Armstrong, W J Locke, A L Statham, H French, R Pidsley, F Valdes-Mora and 2 more

Open access · bronzeAbstract read
PubMed Publisher
In one paragraph

Article in Oncogene, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 46 papers.

0numbers the graph read from it
0cells of the map it votes in
46citing papers in PubMed
4.5field-weighted citation impact, top 5% 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

46 citing papers in PubMed, 93 citations in OpenAlex.

  1. Article
  2. Article
  3. MBD1-Mediated SDHD Methylation Aggravates Preeclampsia Progression via Triggering Mitochondrial Dysfunction.FASEB journal : official publication of the Federation of American Societies for Experimental Biology · 2026
    Article
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  15. The roles of chromatin regulatory factors in endometriosis.Journal of assisted reproduction and genetics · 2024
    Review
  16. Review
  17. Article
  18. Article
  19. Nucleosome destabilization by polyamines.Archives of biochemistry and biophysics · 2022
    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

12 authors at 2 institutions in 1 country.

C StirzakerEpigenetics Research Laboratory, Genomics and Epigenetics Division, Garvan Institute of Medical Research, Sydney, New South Wales, Australia.
J Z SongEpigenetics Research Laboratory, Genomics and Epigenetics Division, Garvan Institute of Medical Research, Sydney, New South Wales, Australia.
W NgEpigenetics Research Laboratory, Genomics and Epigenetics Division, Garvan Institute of Medical Research, Sydney, New South Wales, Australia.
Q DuEpigenetics Research Laboratory, Genomics and Epigenetics Division, Garvan Institute of Medical Research, Sydney, New South Wales, Australia.
N J ArmstrongMathematics and Statistics, SEIT, Murdoch University, Murdoch, Western Australia, Australia.ORCID 0000-0002-4477-293X
W J LockeEpigenetics Research Laboratory, Genomics and Epigenetics Division, Garvan Institute of Medical Research, Sydney, New South Wales, Australia.
A L StathamEpigenetics Research Laboratory, Genomics and Epigenetics Division, Garvan Institute of Medical Research, Sydney, New South Wales, Australia.
H FrenchEpigenetics Research Laboratory, Genomics and Epigenetics Division, Garvan Institute of Medical Research, Sydney, New South Wales, Australia.ORCID 0000-0001-7464-6929
R PidsleyEpigenetics Research Laboratory, Genomics and Epigenetics Division, Garvan Institute of Medical Research, Sydney, New South Wales, Australia.
F Valdes-MoraEpigenetics Research Laboratory, Genomics and Epigenetics Division, Garvan Institute of Medical Research, Sydney, New South Wales, Australia.
E ZotenkoEpigenetics Research Laboratory, Genomics and Epigenetics Division, Garvan Institute of Medical Research, Sydney, New South Wales, Australia.
S J ClarkEpigenetics Research Laboratory, Genomics and Epigenetics Division, Garvan Institute of Medical Research, Sydney, New South Wales, Australia.
Garvan Institute of Medical Research · AUMurdoch University · AU

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

Cancer is characterised by DNA hypermethylation and gene silencing of CpG island-associated promoters, including tumour-suppressor genes. The methyl-CpG-binding domain (MBD) family of proteins bind to methylated DNA and can aid in the mediation of gene silencing through interaction with histone deacetylases and histone methyltransferases. However, the mechanisms responsible for eliciting CpG island hypermethylation in cancer, and the potential role that MBD proteins play in modulation of the methylome remain unclear. Our previous work demonstrated that MBD2 preferentially binds to the hypermethylated GSTP1 promoter CpG island in prostate cancer cells. Here, we use functional genetic approaches to investigate if MBD2 plays an active role in reshaping the DNA methylation landscape at this locus and genome-wide. First, we show that loss of MBD2 results in inhibition of both maintenance and spread of de novo methylation of a transfected construct containing the GSTP1 promoter CpG island in prostate cancer cells and Mbd2-/- mouse fibroblasts. De novo methylation was rescued by transient expression of Mbd2 in Mbd2-/- cells. Second, we show that MBD2 depletion triggers significant hypomethylation genome-wide in prostate cancer cells with concomitant loss of MBD2 binding at promoter and enhancer regulatory regions. Finally, CpG islands and shores that become hypomethylated after MBD2 depletion in LNCaP cancer cells show significant hypermethylation in clinical prostate cancer samples, highlighting a potential active role of MBD2 in promoting cancer-specific hypermethylation. Importantly, co-immunoprecipiation of MBD2 shows that MBD2 associates with DNA methyltransferase enzymes 1 and 3A. Together our results demonstrate that MBD2 has a critical role in 'rewriting' the cancer methylome at specific regulatory regions.

Indexed as

CpG IslandsDNA MethylationAnimalsCell Line, TumorCluster AnalysisDNA-Binding ProteinsDNA-Cytosine MethylasesFibroblastsGene Expression ProfilingGene Expression Regulation, NeoplasticGene Knockout TechniquesGlutathione S-Transferase piHumansMiceNeoplasmsPromoter Regions, GeneticDNA-Binding ProteinsDNA-Cytosine MethylasesGlutathione S-Transferase piMBD2 protein

Identifiers

PMID27593931
OpenAlexW2507741532

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.