Evidence map›Paper›PMID 36732350›Full record

ArticleCommunications biology2023

Genome-wide deposition of 6-methyladenine in human DNA reduces the viability of HEK293 cells and directly influences gene expression.

Julian Broche, Anja R Köhler, Fiona Kühnel, Bernd Osteresch, Thyagarajan T Chandrasekaran, Sabrina Adam, Jens Brockmeyer, Albert Jeltsch

Open access · goldAbstract read
In one paragraph

Article in Communications biology, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 5 papers.

0numbers the graph read from it
0cells of the map it votes in
5citing papers in PubMed
0.8field-weighted citation impact, top 28% 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

5 citing papers in PubMed, 5 citations in OpenAlex.

  1. Review
  2. Deep Learning-Based Ion Channel Kinetics Analysis for Automated Patch Clamp Recording.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2025
    Article
  3. Article
  4. Article
  5. 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

8 authors at 1 institution in 1 country.

Julian BrocheInstitute of Biochemistry and Technical Biochemistry, Department of Biochemistry, University of Stuttgart, Allmandring 31, 70569, Stuttgart, Germany.
Anja R KöhlerInstitute of Biochemistry and Technical Biochemistry, Department of Biochemistry, University of Stuttgart, Allmandring 31, 70569, Stuttgart, Germany.
Fiona KühnelInstitute of Biochemistry and Technical Biochemistry, Department of Biochemistry, University of Stuttgart, Allmandring 31, 70569, Stuttgart, Germany.
Bernd OstereschInstitute of Biochemistry and Technical Biochemistry, Department of Food Chemistry, University of Stuttgart, Allmandring 5b, 70569, Stuttgart, Germany.
Thyagarajan T ChandrasekaranInstitute of Biochemistry and Technical Biochemistry, Department of Biochemistry, University of Stuttgart, Allmandring 31, 70569, Stuttgart, Germany.
Sabrina AdamInstitute of Biochemistry and Technical Biochemistry, Department of Biochemistry, University of Stuttgart, Allmandring 31, 70569, Stuttgart, Germany.
Jens BrockmeyerInstitute of Biochemistry and Technical Biochemistry, Department of Food Chemistry, University of Stuttgart, Allmandring 5b, 70569, Stuttgart, Germany.
Albert JeltschInstitute of Biochemistry and Technical Biochemistry, Department of Biochemistry, University of Stuttgart, Allmandring 31, 70569, Stuttgart, Germany. albert.jeltsch@ibtb.uni-stuttgart.de.ORCID 0000-0001-6113-9290
University of Stuttgart · DE

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

While cytosine-C5 methylation of DNA is an essential regulatory system in higher eukaryotes, the presence and relevance of 6-methyladenine (m6dA) in human cells is controversial. To study the role of m6dA in human DNA, we introduced it in human cells at a genome-wide scale at GANTC and GATC sites by expression of bacterial DNA methyltransferases and observed concomitant reductions in cell viability, in particular after global GANTC methylation. We identified several genes that are directly regulated by m6dA in a GANTC context. Upregulated genes showed m6dA-dependent reduction of H3K27me3 suggesting that the PRC2 complex is inhibited by m6dA. Genes downregulated by m6dA showed enrichment of JUN family transcription factor binding sites. JUN binds m6dA containing DNA with reduced affinity suggesting that m6dA can reduce the recruitment of JUN transcription factors to target genes. Our study documents that global introduction of m6dA in human DNA has physiological effects. Furthermore, we identified a set of target genes which are directly regulated by m6dA in human cells, and we defined two molecular pathways with opposing effects by which artificially introduced m6dA in GANTC motifs can directly control gene expression and phenotypes of human cells.

Indexed as

DNADNA MethylationAdenineGene ExpressionHEK293 CellsHumans6-methyladenineAdenineDNA

Identifiers

PMID36732350
PMCPMC9895073
OpenAlexW4318981915

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.