Evidence map›Paper›PMID 36347867›Full record

ArticleNature communications2022

Cell division drives DNA methylation loss in late-replicating domains in primary human cells.

Jamie L Endicott, Paula A Nolte, Hui Shen, Peter W Laird

Open access · goldAbstract read
In one paragraph

Article in Nature communications, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 58 papers.

0numbers the graph read from it
0cells of the map it votes in
58citing papers in PubMed
7.1field-weighted citation impact, top 2% 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

58 citing papers in PubMed, 77 citations in OpenAlex.

  1. Epigenetic regulation of transgenes.Journal of biotechnology · 2026
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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

4 authors at 1 institution in 1 country.

Jamie L EndicottDepartment of Epigenetics, Van Andel Institute, Grand Rapids, MI, USA.
Paula A NolteDepartment of Epigenetics, Van Andel Institute, Grand Rapids, MI, USA.
Hui ShenDepartment of Epigenetics, Van Andel Institute, Grand Rapids, MI, USA. hui.shen@vai.org.
Peter W LairdDepartment of Epigenetics, Van Andel Institute, Grand Rapids, MI, USA. peter.laird@vai.org.ORCID 0000-0001-9117-3641
Van Andel Institute · US

Funding

Progressive DNA Hypomethylation as a Measure of Mitotic History and Potential Contributor to Replicative Senescence.R01AG066764 · NIA · VAN ANDEL RESEARCH INSTITUTE · PI LAIRD, PETER W · 2020 to 2024
$3.0M
NIA NIH HHS R01 AG066764
6 · The paper itself

Abstract

DNA methylation undergoes dramatic age-related changes, first described more than four decades ago. Loss of DNA methylation within partially methylated domains (PMDs), late-replicating regions of the genome attached to the nuclear lamina, advances with age in normal tissues, and is further exacerbated in cancer. We present here experimental evidence that this DNA hypomethylation is directly driven by proliferation-associated DNA replication. Within PMDs, loss of DNA methylation at low-density CpGs in A:T-rich immediate context (PMD solo-WCGWs) tracks cumulative population doublings in primary cell culture. Cell cycle deceleration results in a proportional decrease in the rate of DNA hypomethylation. Blocking DNA replication via Mitomycin C treatment halts methylation loss. Loss of methylation continues unabated after TERT immortalization until finally reaching a severely hypomethylated equilibrium. Ambient oxygen culture conditions increases the rate of methylation loss compared to low-oxygen conditions, suggesting that some methylation loss may occur during unscheduled, oxidative damage repair-associated DNA synthesis. Finally, we present and validate a model to estimate the relative cumulative replicative histories of human cells, which we call "RepliTali" (Replication Times Accumulated in Lifetime).

Indexed as

DNA MethylationGenomeCell DivisionDNAHumansOxygenDNAOxygen

Identifiers

PMID36347867
PMCPMC9643452
OpenAlexW4308568985

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.