ArticleGenes2018
Linking DNA Damage and Age-Related Promoter DNA Hyper-Methylation in the Intestine.
Article in Genes, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 10 papers.
What it found
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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.
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.
Who cites it
10 citing papers in PubMed, 15 citations in OpenAlex.
- Cellular stress and epigenetic regulation in adult stem cells.Life science alliance · 2024Review
- A ROS-responsive hydrogel incorporated with dental follicle stem cell-derived small extracellular vesicles promotes dental pulp repair by ameliorating oxidative stress.Bioactive materials · 2024Article
- Review
- Systems Modeling to Quantify Safety Risks in Early Drug Development: Using Bifurcation Analysis and Agent-Based Modeling as Examples.The AAPS journal · 2021Review
- Fighting Against Promoter DNA Hyper-Methylation: Protective Histone Modification Profiles of Stress-Resistant Intestinal Stem Cells.International journal of molecular sciences · 2020Article
- Epigenetic Aging: More Than Just a Clock When It Comes to Cancer.Cancer research · 2020Review
- Chromatin Remodeling and Epigenetic Regulation in Plant DNA Damage Repair.International journal of molecular sciences · 2019Review
- Loss of Msh2 and a single-radiation hit induce common, genome-wide, and persistent epigenetic changes in the intestine.Clinical epigenetics · 2019Article
- Extracellular Spermine Activates DNA Methyltransferase 3A and 3B.International journal of molecular sciences · 2019Article
- Polyamine Metabolism and Gene Methylation in Conjunction with One-Carbon Metabolism.International journal of molecular sciences · 2018Review
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
3 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Aberrant DNA methylation in stem cells is a hallmark of aging and tumor development. Here, we explore whether and how DNA damage repair might impact on these time-dependent changes, in particular in proliferative intestinal stem cells. We introduce a 3D multiscale computer model of intestinal crypts enabling simulation of aberrant DNA and histone methylation of gene promoters during aging. We assume histone state-dependent activity of de novo DNA methyltransferases (DNMTs) and methylation-dependent binding of maintenance DNMTs to CpGs. We simulate aging with and without repeated DNA repair. Motivated by recent findings on the histone demethylase KDM2b, we consider that DNA repair is associated with chromatin opening and improved recruitment of de novo DNMTs. Our results suggest that methylation-dependent binding of maintenance DNMTs to CpGs, establishing bistable DNA methylation states, is a prerequisite to promoter hyper-methylation following DNA repair. With this, the transient increase in de novo DNMT activity during repair can induce switches from low to high methylation states. These states remain stable after repair, leading to an epigenetic drift. The switches are most frequent in genes with H3K27me3 modified promoters. Our model provides a mechanistic explanation on how even successful DNA repair might confer long term changes of the epigenome.
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Registered trials
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.