ArticleDevelopment (Cambridge, England)2015
DNA hypomethylation induces a DNA replication-associated cell cycle arrest to block hepatic outgrowth in uhrf1 mutant zebrafish embryos.
Article in Development (Cambridge, England), 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 35 papers.
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Who cites it
35 citing papers in PubMed, 54 citations in OpenAlex.
- DNA methylation protects cancer cells against senescence.Nature communications · 2025Article
- In toto live imaging of Erk signaling dynamics in developing zebrafish hepatocytes.Developmental biology · 2025Article
- Epigenetic Disordering Drives Stemness, Senescence Escape and Tumor Heterogeneity.bioRxiv : the preprint server for biology · 2024Article
- DNA hypomethylation activates Cdk4/6 and Atr to induce DNA replication and cell cycle arrest to constrain liver outgrowth in zebrafish.Nucleic acids research · 2024Article
- Review
- Novel UHRF1-MYC Axis in Acute Lymphoblastic Leukemia.Cancers · 2022Article
- DNA methylation maintenance at the p53 locus initiates biliary-mediated liver regeneration.NPJ Regenerative medicine · 2022Article
- Overexpression of a Gene Encoding Trigonelline Synthase fromPlants (Basel, Switzerland) · 2022Article
- Article
- Chromatin states shaped by an epigenetic code confer regenerative potential to the mouse liver.Nature communications · 2021Article
- The multi-functionality of UHRF1: epigenome maintenance and preservation of genome integrity.Nucleic acids research · 2021Review
- Article
- Article
- dnmt1 function is required to maintain retinal stem cells within the ciliary marginal zone of the zebrafish eye.Scientific reports · 2020Article
- The methylation status of the embryonic limb skeletal progenitors determines their cell fate in chicken.Communications biology · 2020Article
- TET methylcytosine oxidases: new insights from a decade of research.Journal of biosciences · 2020Review
- Epigenetic factors Dnmt1 and Uhrf1 coordinate intestinal development.Developmental biology · 2019Article
- Epigenetic Compensation Promotes Liver Regeneration.Developmental cell · 2019Article
- UHRF genes regulate programmed interdigital tissue regression and chondrogenesis in the embryonic limb.Cell death & disease · 2019Article
- Inorganic arsenic causes fatty liver and interacts with ethanol to cause alcoholic liver disease in zebrafish.Disease models & mechanisms · 2018Article
Corrections and comments
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Authors and funding
7 authors at 1 institution in 2 countries.
Funding
Abstract
UHRF1 (ubiquitin-like, containing PHD and RING finger domains, 1) recruits DNMT1 to hemimethylated DNA during replication and is essential for maintaining DNA methylation. uhrf1 mutant zebrafish have global DNA hypomethylation and display embryonic defects, including a small liver, and they die as larvae. We make the surprising finding that, despite their reduced organ size, uhrf1 mutants express high levels of genes controlling S-phase and have many more cells undergoing DNA replication, as measured by BrdU incorporation. In contrast to wild-type hepatocytes, which are continually dividing during hepatic outgrowth and thus dilute the BrdU label, uhrf1 mutant hepatocytes retain BrdU throughout outgrowth, reflecting cell cycle arrest. Pulse-chase-pulse experiments with BrdU and EdU, and DNA content analysis indicate that uhrf1 mutant cells undergo DNA re-replication and that apoptosis is the fate of many of the re-replicating and arrested hepatocytes. Importantly, the DNA re-replication phenotype and hepatic outgrowth failure are preceded by global loss of DNA methylation. Moreover, uhrf1 mutants are phenocopied by mutation of dnmt1, and Dnmt1 knockdown in uhrf1 mutants enhances their small liver phenotype. Together, these data indicate that unscheduled DNA replication and failed cell cycle progression leading to apoptosis are the mechanisms by which DNA hypomethylation prevents organ expansion in uhrf1 mutants. We propose that cell cycle arrest leading to apoptosis is a strategy that restricts propagation of epigenetically damaged cells during embryogenesis.
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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.