Evidence map›Paper›PMID 32663196›Full record

ArticleThe Journal of clinical investigation2020

TET repression and increased DNMT activity synergistically induce aberrant DNA methylation.

Hideyuki Takeshima, Tohru Niwa, Satoshi Yamashita, Takeji Takamura-Enya, Naoko Iida, Mika Wakabayashi, Sohachi Nanjo, Masanobu Abe, Toshiro Sugiyama, Young-Joon Kim and 1 more

Open access · bronzeAbstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in The Journal of clinical investigation, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 48 papers.

0numbers the graph read from it
0cells of the map it votes in
48citing papers in PubMed
4.7field-weighted citation impact, top 4% 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

48 citing papers in PubMed, 83 citations in OpenAlex.

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  9. Concurrent hypermethylation of CpG islands and hypomethylation of CpG-poor regions are associated with gastric cancer risk after Helicobacter pylori eradication.Gastric cancer : official journal of the International Gastric Cancer Association and the Japanese Gastric Cancer Association · 2025
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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

11 authors at 4 institutions in 2 countries.

Hideyuki TakeshimaDivision of Epigenomics, National Cancer Center Research Institute, Tokyo, Japan.
Tohru NiwaDivision of Epigenomics, National Cancer Center Research Institute, Tokyo, Japan.
Satoshi YamashitaDivision of Epigenomics, National Cancer Center Research Institute, Tokyo, Japan.
Takeji Takamura-EnyaDepartment of Applied Chemistry, Kanagawa Institute of Technology, Kanagawa, Japan.
Naoko IidaDivision of Epigenomics, National Cancer Center Research Institute, Tokyo, Japan.
Mika WakabayashiDivision of Epigenomics, National Cancer Center Research Institute, Tokyo, Japan.
Sohachi NanjoThird Department of Internal Medicine, University of Toyama, Toyama, Japan.
Masanobu AbeDepartment of Oral and Maxillofacial Surgery, University of Tokyo Hospital, Tokyo, Japan.
Toshiro SugiyamaThird Department of Internal Medicine, University of Toyama, Toyama, Japan.
Young-Joon KimDepartment of Biochemistry, College of Life Science and Biotechnology, Yonsei University, Seoul, Korea.
Toshikazu UshijimaDivision of Epigenomics, National Cancer Center Research Institute, Tokyo, Japan.
University of Toyama · JPKanagawa Institute of Technology · JPUniversity of Tokyo Hospital · JPYonsei University · KR

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

Chronic inflammation is deeply involved in various human disorders, such as cancer, neurodegenerative disorders, and metabolic disorders. Induction of epigenetic alterations, especially aberrant DNA methylation, is one of the major mechanisms, but how it is induced is still unclear. Here, we found that expression of TET genes, methylation erasers, was downregulated in inflamed mouse and human tissues, and that this was caused by upregulation of TET-targeting miRNAs such as MIR20A, MIR26B, and MIR29C, likely due to activation of NF-κB signaling downstream of IL-1β and TNF-α. However, TET knockdown induced only mild aberrant methylation. Nitric oxide (NO), produced by NOS2, enhanced enzymatic activity of DNA methyltransferases (DNMTs), methylation writers, and NO exposure induced minimal aberrant methylation. In contrast, a combination of TET knockdown and NO exposure synergistically induced aberrant methylation, involving genomic regions not methylated by either alone. The results showed that a vicious combination of TET repression, due to NF-κB activation, and DNMT activation, due to NO production, is responsible for aberrant methylation induction in human tissues.

Indexed as

DNA MethylationAnimalsDioxygenasesDisease Models, AnimalDNA Modification MethylasesDown-RegulationEpigenesis, GeneticGastritisHelicobacter felisHelicobacter InfectionsHelicobacter pyloriHumansInflammationMaleMiceMice, Inbred C57BLDioxygenasesDNA Modification MethylasesMicroRNAsNF-kappa BNitric OxideEpigeneticsOncology

Identifiers

PMID32663196
PMCPMC7524486
OpenAlexW3043723571

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.