Evidence map›Paper›PMID 35987848›Full record

ArticleClinical epigenetics2022

Genomic targets and selective inhibition of DNA methyltransferase isoforms.

Chanachai Sae-Lee, Timothy M Barrow, Elena Colicino, Si Ho Choi, Yoana Rabanal-Ruiz, Daniel Green, Viktor I Korolchuk, John C Mathers, Hyang-Min Byun

Open access · goldAbstract read
In one paragraph

Article in Clinical epigenetics, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 13 papers.

0numbers the graph read from it
0cells of the map it votes in
13citing papers in PubMed
1.4field-weighted citation impact, top 19% 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

13 citing papers in PubMed, 16 citations in OpenAlex.

  1. DNA Methylation Dynamics inBiomolecules · 2026
    Article
  2. Article
  3. Article
  4. Article
  5. Epigenetic networks coordinate DNA methylation across the genome.Molecular therapy : the journal of the American Society of Gene Therapy · 2025
    Review
  6. Article
  7. Epigenetic Consequences of In Utero PFAS Exposure: Implications for Development and Long-Term Health.International journal of environmental research and public health · 2025
    Review
  8. Article
  9. Investigation methylation status of tumor suppressor geneMolecular biology research communications · 2025
    Article
  10. Review
  11. Dnmt3a1 regulates hippocampus-dependent memory via the downstream target Nrp1.Neuropsychopharmacology : official publication of the American College of Neuropsychopharmacology · 2024
    Article
  12. Article
  13. 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

9 authors at 5 institutions in 4 countries.

Chanachai Sae-LeeHuman Nutrition Research Centre, Centre for Healthier Lives, Population Health Sciences Institute, Newcastle University, Newcastle upon Tyne, UK. chanachai.sae@mahidol.ac.th.
Timothy M BarrowFaculty of Health Sciences and Wellbeing, University of Sunderland, Sunderland, UK.
Elena ColicinoDepartment of Environmental Medicine and Public Health, Icahn School of Medicine at Mount Sinai, New York City, USA.
Si Ho ChoiResearch Center, Dongnam Institute of Radiological and Medical Sciences, Busan, 46033, Republic of Korea.
Yoana Rabanal-RuizBiosciences Institute, Faculty of Medical Sciences, Newcastle University, Newcastle upon Tyne, UK.
Daniel GreenInstitute of Life Course and Medical Sciences, Faculty of Health and Life Sciences, University of Liverpool, Liverpool, UK.
Viktor I KorolchukBiosciences Institute, Faculty of Medical Sciences, Newcastle University, Newcastle upon Tyne, UK.
John C MathersHuman Nutrition Research Centre, Centre for Healthier Lives, Population Health Sciences Institute, Newcastle University, Newcastle upon Tyne, UK.
Hyang-Min ByunHuman Nutrition Research Centre, Centre for Healthier Lives, Population Health Sciences Institute, Newcastle University, Newcastle upon Tyne, UK.
Newcastle University · GBDongnam Institute of Radiological & Medical Sciences · KRIcahn School of Medicine at Mount Sinai · USUniversity of Liverpool · GBUniversity of Sunderland · GB

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

backgroundDNA methylation in the human genome is established and maintained by DNA methyltransferases (DNMTs). DNMT isoforms show differential expression by cell lineage and during development, but much remains to be elucidated about their shared and unique genomic targets.

resultsWe examined changes in the epigenome following overexpression of 13 DNMT isoforms in HEK293T cells. We observed increased methylation (Δβ > 0.2) at 43,405 CpG sites, with expression of DNMT3A2, DNMTΔ3B4 and DNMTΔ3B2 associated with the greatest impact. De novo methylation occurred primarily within open sea regions and at loci with intermediate methylation levels (β: 0.2-0.6). 53% of differentially methylated loci showed specificity towards a single DNMT subfamily, primarily DNMTΔ3B and DNMT3A and 39% towards a single isoform. These loci were significantly enriched for pathways related to neuronal development (DNMTΔ3B4), calcium homeostasis (DNMTΔ3B3) and ion transport (DNMT3L). Repetitive elements did not display differential sensitivity to overexpressed DNMTs, but hypermethylation of Alu elements was associated with their evolutionary age following overexpression of DNMT3A2, DNMT3B1, DNMT3B2 and DNMT3L. Differential methylation (Δβ > 0.1) was observed at 121 of the 353 loci associated with the Horvath 'epigenetic clock' model of ageing, with 51 showing isoform specificity, and was associated with reduction of epigenetic age by 5-15 years following overexpression of seven isoforms. Finally, we demonstrate the potential for dietary constituents to modify epigenetic marks through isoform-specific inhibition of methylation activity.

conclusionsOur results provide insight into regions of the genome methylated uniquely by specific DNMT isoforms and demonstrate the potential for dietary intervention to modify the epigenome.

Indexed as

DNA (Cytosine-5-)-MethyltransferasesDNA MethylationDNA Modification MethylasesGenomeHEK293 CellsHumansProtein IsoformsDNA (Cytosine-5-)-MethyltransferasesDNA Modification MethylasesProtein IsoformsDietary constituentsDNA methylationDNA methyltransferasesDNMT isoformsEpigenetic clockEpigenomeRepetitive elements

Identifiers

PMID35987848
PMCPMC9392947
OpenAlexW4292440709

What OpenQuestion holds

Textmetadata
LicenceCC BY
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.