Evidence map›Paper›PMID 39617792›Full record

ArticleNature communications2024

SAM-DNMT3A, a strategy for induction of genome-wide DNA methylation, identifies DNA methylation as a vulnerability in ER-positive breast cancers.

Mahnaz Hosseinpour, Xinqi Xi, Ling Liu, Luis Malaver-Ortega, Laura Perlaza-Jimenez, Jihoon E Joo, Harrison M York, Jonathan Beesley, C Elizabeth Caldon, Pierre-Antoine Dugué and 4 more

Abstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Nature communications, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 2 papers.

0numbers the graph read from it
0cells of the map it votes in
2citing papers in PubMed
–field-weighted citation impact
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

2 citing papers in PubMed.

  1. Review
  2. 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

14 authors.

Mahnaz HosseinpourDepartment of Biochemistry and Molecular Biology and Cancer program, Biomedicine Discovery Institute, Monash University, Melbourne, VIC, Australia.ORCID 0000-0003-4787-1965
Xinqi XiDepartment of Biochemistry and Molecular Biology and Cancer program, Biomedicine Discovery Institute, Monash University, Melbourne, VIC, Australia.
Ling LiuDepartment of Biochemistry and Molecular Biology and Cancer program, Biomedicine Discovery Institute, Monash University, Melbourne, VIC, Australia.ORCID 0009-0001-3822-1111
Luis Malaver-OrtegaFunctional Genomics Platform, Monash University, Melbourne, VIC, Australia.
Laura Perlaza-JimenezDepartment of Biochemistry and Molecular Biology and Cancer program, Biomedicine Discovery Institute, Monash University, Melbourne, VIC, Australia.
Jihoon E JooDepartment of Clinical Pathology, Melbourne Medical School, The University of Melbourne, Melbourne, VIC, Australia.
Harrison M YorkDepartment of Anatomy and Developmental Biology, Biomedicine Discovery Institute, Monash University, Melbourne, VIC, Australia.ORCID 0000-0002-4534-8188
Jonathan BeesleyCancer Program, QIMR Berghofer Medical Research Institute, Brisbane, QLD, Australia.
C Elizabeth CaldonThe Kinghorn Cancer Centre, Garvan Institute of Medical Research, Sydney, NSW, Australia.ORCID 0000-0003-1392-3472
Pierre-Antoine DuguéPrecision Medicine, School of Clinical Sciences at Monash Health, Monash University, Melbourne, VIC, Australia.ORCID 0000-0003-2736-3023
James G DowtyCentre for Epidemiology and Biostatistics, Melbourne School of Population and Global Health, The University of Melbourne, Melbourne, VIC, Australia.ORCID 0000-0003-2383-0886
Senthil ArumugamDepartment of Anatomy and Developmental Biology, Biomedicine Discovery Institute, Monash University, Melbourne, VIC, Australia.ORCID 0000-0001-6733-4679
Melissa C SoutheyPrecision Medicine, School of Clinical Sciences at Monash Health, Monash University, Melbourne, VIC, Australia. melissa.southey@monash.edu.ORCID 0000-0002-6313-9005
Joseph RosenbluhDepartment of Biochemistry and Molecular Biology and Cancer program, Biomedicine Discovery Institute, Monash University, Melbourne, VIC, Australia. sefi.rosenbluh@monash.edu.ORCID 0000-0001-9815-8049

Funding

Department of Health | National Health and Medical Research Council (NHMRC) 2011329Victorian Cancer Agency (VCA) MCRF20035
6 · The paper itself

Abstract

DNA methylation is an epigenetic mark that plays a critical role in regulating gene expression. DNA methyltransferase (DNMT) inhibitors, inhibit global DNA methylation and have been a key tool in studies of DNA methylation. A major bottleneck is the lack of tools to induce global DNA methylation. Here, we engineered a CRISPR based approach, that we initially designed, to enable site-specific DNA methylation. Using the synergistic activation mediator (SAM) system, we unexpectedly find that regardless of the targeted sequence any sgRNA induces global genome-wide DNA methylation. We term this method SAM-DNMT3A and show that induction of global DNA methylation is a unique vulnerability in ER-positive breast cancer suggesting a therapeutic approach. Our findings highlight the need of caution when using CRISPR based approaches for inducing DNA methylation and demonstrate a method for global induction of DNA methylation.

Indexed as

Breast NeoplasmsDNA (Cytosine-5-)-MethyltransferasesDNA MethylationDNA Methyltransferase 3ACell Line, TumorCRISPR-Cas SystemsEpigenesis, GeneticFemaleGene Expression Regulation, NeoplasticHumansMCF-7 CellsReceptors, EstrogenRNA, Guide, CRISPR-Cas SystemsDNA (Cytosine-5-)-MethyltransferasesDNA Methyltransferase 3ADNMT3A protein, humanReceptors, EstrogenRNA, Guide, CRISPR-Cas Systems

Identifiers

PMID39617792
PMCPMC11609277

What OpenQuestion holds

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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.