ArticleHepatology (Baltimore, Md.)2016
DNMT1 is a required genomic regulator for murine liver histogenesis and regeneration.
Article in Hepatology (Baltimore, Md.), 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 31 papers.
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Who cites it
31 citing papers in PubMed, 64 citations in OpenAlex.
- Epigenetic dynamics of cellular senescence: From mechanistic insights to precision senotherapy.Chinese medical journal · 2026Review
- Spatial hepatology: Decoding liver zonation for metabolic and regenerative therapeutics (Review).International journal of molecular medicine · 2026Review
- FOXM1 influences DNA methylation to augment TACC3 alternative splicing directed by KAT2A in hepatocellular carcinoma.Clinical and molecular hepatology · 2026Article
- Genetic and pharmaceutical manipulation of H3K9 methyltransferase Suv39h1 promotes liver regeneration by unleashing HMGB2 transcription.Experimental & molecular medicine · 2026Article
- Roles of different methylation modifications in cardiovascular disease.Frontiers of medicine · 2025Review
- Evolutionary and structural insights into DNMTs and TETs: decoding their functional heterogeneity and oncogenic roles in methylation regulation.BMC molecular and cell biology · 2025Article
- Abundant repressor binding sites in human enhancers are associated with the fine-tuning of gene regulation.iScience · 2025Article
- DNMT1 prolonged absence is a tunable cellular stress that triggers cell proliferation arrest to protect from major DNA methylation loss.Cellular and molecular life sciences : CMLS · 2024Article
- Cellular Senescence in Acute Liver Injury: What Happens to the Young Liver?Aging and disease · 2024Review
- A biomarker framework for liver aging: the Aging Biomarker Consortium consensus statement.Life medicine · 2024Article
- In-organoid single-cell CRISPR screening reveals determinants of hepatocyte differentiation and maturation.Genome biology · 2023Article
- PD-L1 Downregulation and DNA Methylation Inhibition for Molecular Therapy against Cancer Stem Cells in Hepatocellular Carcinoma.International journal of molecular sciences · 2023Article
- Distinct hepatocyte identities in liver homeostasis and regeneration.JHEP reports : innovation in hepatology · 2023Review
- UHRF1 inhibition epigenetically reprograms cancer stem cells to suppress the tumorigenic phenotype of hepatocellular carcinoma.Cell death & disease · 2023Article
- Epigenetic Mechanisms Contribute to Intraindividual Variations of Drug Metabolism Mediated by Cytochrome P450 Enzymes.Drug metabolism and disposition: the biological fate of chemicals · 2023Review
- Dnmt1 is required for the development of auditory organs via cell cycle arrest and Fgf signalling.Cell proliferation · 2022Article
- DNA methylation maintenance at the p53 locus initiates biliary-mediated liver regeneration.NPJ Regenerative medicine · 2022Article
- DNA methyltransferase 1 inhibits microRNA-497 and elevates GPRC5A expression to promote chemotherapy resistance and metastasis in breast cancer.Cancer cell international · 2022Article
- ZNF191 alters DNA methylation and activates the PI3K-AKT pathway in hepatoma cells via transcriptional regulation of DNMT1.Cancer medicine · 2022Article
- Liver Regeneration: Changes in Oxidative Stress, Immune System, Cytokines, and Epigenetic Modifications Associated with Aging.Oxidative medicine and cellular longevity · 2022Review
Corrections and comments
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Authors and funding
10 authors at 3 institutions in 3 countries.
Funding
Abstract
unlabelledDNA methyltransferase 1 (DNMT1) is an essential regulator maintaining both epigenetic reprogramming during DNA replication and genome stability. We investigated the role of DNMT1 in the regulation of postnatal liver histogenesis under homeostasis and stress conditions. We generated Dnmt1 conditional knockout mice (Dnmt1(Δalb) ) by crossing Dnmt1(fl/fl) with albumin-cyclization recombination transgenic mice. Serum, liver tissues, and primary hepatocytes were collected from 1-week-old to 20-week old mice. The Dnmt1(Δalb) phenotype was assessed by histology, confocal and electron microscopy, biochemistry, as well as transcriptome and methylation profiling. Regenerative growth was induced by partial hepatectomy and exposure to carbon tetrachloride. The impact of Dnmt1 knockdown was also analyzed in hepatic progenitor cell lines; proliferation, apoptosis, DNA damage, and sphere formation were assessed. Dnmt1 loss in postnatal hepatocytes caused global hypomethylation, enhanced DNA damage response, and initiated a senescence state causing a progressive inability to maintain tissue homeostasis and proliferate in response to injury. The liver regenerated through activation and repopulation from progenitors due to lineage-dependent differences in albumin-cyclization recombination expression, providing a basis for selection of less mature and therefore less damaged hepatic progenitor cell progeny. Consistently, efficient knockdown of Dnmt1 in cultured hepatic progenitor cells caused severe DNA damage, cell cycle arrest, senescence, and cell death. Mx1-cyclization recombination-driven deletion of Dnmt1 in adult quiescent hepatocytes did not affect liver homeostasis.
conclusionThese results establish the indispensable role of DNMT1-mediated epigenetic regulation in postnatal liver growth and regeneration; Dnmt1(Δalb) mice provide a unique experimental model to study the role of senescence and the contribution of progenitor cells to physiological and regenerative liver growth. (Hepatology 2016;64:582-598).
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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.