Evidence map›Paper›PMID 34086943›Full record

ArticleNucleic acids research2021

CD44 alternative splicing senses intragenic DNA methylation in tumors via direct and indirect mechanisms.

Eric Batsché, Jia Yi, Oriane Mauger, Etienne Kornobis, Benjamin Hopkins, Charlotte Hanmer-Lloyd, Christian Muchardt

Open access · goldAbstract read
In one paragraph

Article in Nucleic acids research, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 18 papers.

0numbers the graph read from it
0cells of the map it votes in
18citing 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

18 citing papers in PubMed, 25 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

7 authors at 1 institution in 2 countries.

Eric BatschéEpigenetics and RNA metabolism in human diseases. CNRS UMR8256 - Biological Adaptation and Ageing. Institut de Biologie Paris-Seine. Sciences Sorbonne Université. 7-9 Quai Saint Bernard, 75005 Paris, France.ORCID 0000-0002-5145-5270
Jia YiUnité de Régulation Epigénétique, Institut Pasteur, Paris, France.ORCID 0000-0003-4795-471X
Oriane MaugerUnité de Régulation Epigénétique, Institut Pasteur, Paris, France.ORCID 0000-0003-0158-5875
Etienne KornobisUnité de Régulation Epigénétique, Institut Pasteur, Paris, France.ORCID 0000-0001-7712-8270
Benjamin HopkinsUnité de Régulation Epigénétique, Institut Pasteur, Paris, France.ORCID 0000-0003-1923-0239
Charlotte Hanmer-LloydUnité de Régulation Epigénétique, Institut Pasteur, Paris, France.ORCID 0000-0003-4131-2839
Christian MuchardtEpigenetics and RNA metabolism in human diseases. CNRS UMR8256 - Biological Adaptation and Ageing. Institut de Biologie Paris-Seine. Sciences Sorbonne Université. 7-9 Quai Saint Bernard, 75005 Paris, France.ORCID 0000-0003-0145-4023
Centre National de la Recherche Scientifique · FR

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

DNA methylation (meDNA) is a modulator of alternative splicing, and splicing perturbations are involved in tumorigenesis nearly as frequently as DNA mutations. However, the impact of meDNA on tumorigenesis via splicing-mediated mechanisms has not been thoroughly explored. Here, we found that HCT116 colon carcinoma cells inactivated for the DNA methylases DNMT1/3b undergo a partial epithelial to mesenchymal transition associated with increased CD44 variant exon skipping. These skipping events are directly mediated by the loss of intragenic meDNA and the chromatin factors MBD1/2/3 and HP1γ and are also linked to phosphorylation changes in elongating RNA polymerase II. The role of meDNA in alternative splicing was confirmed by using the dCas9/DNMT3b tool. We further tested whether the meDNA level could have predictive value in the MCF10A model for breast cancer progression and in patients with acute lymphoblastic leukemia (B ALL). We found that a small number of differentially spliced genes, mostly involved in splicing and signal transduction, are correlated with the local modulation of meDNA. Our observations suggest that, although DNA methylation has multiple avenues to affect alternative splicing, its indirect effect may also be mediated through alternative splicing isoforms of these meDNA sensors.

Indexed as

Alternative SplicingDNA MethylationGene Expression Regulation, NeoplasticBreast NeoplasmsCarcinogenesisCell Line, TumorChromobox Protein Homolog 5Chromosomal Proteins, Non-HistoneDNA-Binding ProteinsDNA (Cytosine-5-)-Methyltransferase 1DNA (Cytosine-5-)-MethyltransferasesDNA Methyltransferase 3BEpithelial-Mesenchymal TransitionExonsFemaleHeLa CellsCD44 protein, humanChromobox Protein Homolog 5Chromosomal Proteins, Non-HistoneDNA-Binding ProteinsDNA (Cytosine-5-)-Methyltransferase 1DNA (Cytosine-5-)-MethyltransferasesDNA Methyltransferase 3BDNMT1 protein, humanHyaluronan ReceptorsMBD1 protein, humanRNA Polymerase IITranscription Factors

Identifiers

PMID34086943
PMCPMC8216461
OpenAlexW3165006430

What OpenQuestion holds

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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.