Evidence map›Paper›PMID 37660134›Full record

ArticleNature communications2023

Epigenetic inheritance is unfaithful at intermediately methylated CpG sites.

Amir D Hay, Noah J Kessler, Daniel Gebert, Nozomi Takahashi, Hugo Tavares, Felipe K Teixeira, Anne C Ferguson-Smith

Abstract read
In one paragraph

Article in Nature communications, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 8 papers.

0numbers the graph read from it
0cells of the map it votes in
8citing 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

8 citing papers in PubMed.

  1. Article
  2. Review
  3. Review
  4. Article
  5. Article
  6. Article
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  8. 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

7 authors.

Amir D HayDepartment of Genetics, University of Cambridge, Downing Street, Cambridge, CB2 3EH, UK.ORCID http://orcid.org/0000-0001-9435-2848
Noah J KesslerDepartment of Genetics, University of Cambridge, Downing Street, Cambridge, CB2 3EH, UK.ORCID http://orcid.org/0000-0002-2740-6663
Daniel GebertDepartment of Genetics, University of Cambridge, Downing Street, Cambridge, CB2 3EH, UK.
Nozomi TakahashiDepartment of Genetics, University of Cambridge, Downing Street, Cambridge, CB2 3EH, UK.
Hugo TavaresDepartment of Genetics, University of Cambridge, Downing Street, Cambridge, CB2 3EH, UK.ORCID http://orcid.org/0000-0001-9373-2726
Felipe K TeixeiraDepartment of Genetics, University of Cambridge, Downing Street, Cambridge, CB2 3EH, UK. fk319@cam.ac.uk.ORCID http://orcid.org/0000-0001-7651-1657
Anne C Ferguson-SmithDepartment of Genetics, University of Cambridge, Downing Street, Cambridge, CB2 3EH, UK. afsmith@gen.cam.ac.uk.ORCID http://orcid.org/0000-0002-7608-5894

Funding

Medical Research Council MR/R009791/1Wellcome Trust 210757/Z/18/Z
6 · The paper itself

Abstract

DNA methylation at the CpG dinucleotide is considered a stable epigenetic mark due to its presumed long-term inheritance through clonal expansion. Here, we perform high-throughput bisulfite sequencing on clonally derived somatic cell lines to quantitatively measure methylation inheritance at the nucleotide level. We find that although DNA methylation is generally faithfully maintained at hypo- and hypermethylated sites, this is not the case at intermediately methylated CpGs. Low fidelity intermediate methylation is interspersed throughout the genome and within genes with no or low transcriptional activity, and is not coordinately maintained between neighbouring sites. We determine that the probabilistic changes that occur at intermediately methylated sites are likely due to DNMT1 rather than DNMT3A/3B activity. The observed lack of clonal inheritance at intermediately methylated sites challenges the current epigenetic inheritance model and has direct implications for both the functional relevance and general interpretability of DNA methylation as a stable epigenetic mark.

Indexed as

DNA MethylationNucleotidesBase SequenceCell LineEpigenesis, GeneticNucleotides

Identifiers

PMID37660134
PMCPMC10475082

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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.