ArticleJournal of hematology & oncology2015
DNA methyltransferase 1 functions through C/ebpa to maintain hematopoietic stem and progenitor cells in zebrafish.
Article in Journal of hematology & oncology, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 32 papers.
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Who cites it
32 citing papers in PubMed, 45 citations in OpenAlex.
- Trawling the depths of gene regulation: transcription-factor families orchestrating immunity in teleost fish.Frontiers in immunology · 2026Review
- DNA methyltransferase Dnmt3ba-mediated epigenetic modulation of Integrin signaling is essential for hematopoietic stem and progenitor cell development.Communications biology · 2025Article
- Rnf111 has a pivotal role in regulating development of definitive hematopoietic stem and progenitor cells through the Smad2/3-Gcsfr/NO axis in zebrafish.Haematologica · 2025Article
- Decitabine facilitates thrombopoiesis independent of the thrombopoietin receptor in zebrafish.Blood science (Baltimore, Md.) · 2025Article
- Cebpa is required for haematopoietic stem and progenitor cell generation and maintenance in zebrafish.Open biology · 2024Article
- Traditional Chinese medicine for acute myelocytic leukemia therapy: exploiting epigenetic targets.Frontiers in pharmacology · 2024Review
- DNA methyltransferase-1 in acute myeloid leukaemia: beyond the maintenance of DNA methylation.Annals of medicine · 2022Review
- Hematopoietic Stem and Progenitor Cells (HSPCs) and Hematopoietic Microenvironment: Molecular and Bioinformatic Studies of the Zebrafish Models.International journal of molecular sciences · 2022Review
- DNA methylation safeguards the generation of hematopoietic stem and progenitor cells by repression of Notch signaling.Development (Cambridge, England) · 2022Article
- Tet-mediated DNA demethylation regulates specification of hematopoietic stem and progenitor cells during mammalian embryogenesis.Science advances · 2022Article
- Epigenetic alterations in stem cell ageing-a promising target for age-reversing interventions?Briefings in functional genomics · 2022Review
- Why stem/progenitor cells lose their regenerative potential.World journal of stem cells · 2021Review
- Making Blood from the Vessel: Extrinsic and Environmental Cues Guiding the Endothelial-to-Hematopoietic Transition.Life (Basel, Switzerland) · 2021Review
- Oncogenes, Proto-Oncogenes, and Lineage Restriction of Cancer Stem Cells.International journal of molecular sciences · 2021Review
- Newly identified Gon4l/Udu-interacting proteins implicate novel functions.Scientific reports · 2020Article
- dnmt1 function is required to maintain retinal stem cells within the ciliary marginal zone of the zebrafish eye.Scientific reports · 2020Article
- Mechanisms and rejuvenation strategies for aged hematopoietic stem cells.Journal of hematology & oncology · 2020Review
- Transcriptional Regulation ofGenes · 2020Article
- The eroding chromatin landscape of aging stem cells.Translational medicine of aging · 2020Article
- Epigenetic factors Dnmt1 and Uhrf1 coordinate intestinal development.Developmental biology · 2019Article
Corrections and comments
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Authors and funding
15 authors at 8 institutions in 3 countries.
Funding
Abstract
backgroundDNA methyltransferase 1 (Dnmt1) regulates expression of many critical genes through maintaining parental DNA methylation patterns on daughter DNA strands during mitosis. It is essential for embryonic development and diverse biological processes, including maintenance of hematopoietic stem and progenitor cells (HSPCs). However, the precise molecular mechanism of how Dnmt1 is involved in HSPC maintenance remains unexplored.
methodsAn N-ethyl-N-nitrosourea (ENU)-based genetic screening was performed to identify putative mutants with defects in definitive HSPCs during hematopoiesis in zebrafish. The expression of hematopoietic markers was analyzed via whole mount in situ hybridization assay (WISH). Positional cloning approach was carried out to identify the gene responsible for the defective definitive hematopoiesis in the mutants. Analyses of the mechanism were conducted by morpholino-mediated gene knockdown, mRNA injection rescue assays, anti-phosphorylated histone H3 (pH3) immunostaining and TUNEL assay, quantitative real-time PCR, and bisulfite sequencing analysis.
resultsA heritable mutant line with impaired HSPCs of definitive hematopoiesis was identified. Positional cloning demonstrated that a stop codon mutation was introduced in dnmt1 which resulted in a predicted truncated Dnmt1 lacking the DNA methylation catalytic domain. Molecular analysis revealed that expression of CCAAT/enhancer-binding protein alpha (C/ebpa) was upregulated, which correlated with hypomethylation of CpG islands in the regulation regions of cebpa gene in Dnmt1 deficient HSPCs. Overexpression of a transcriptional repressive SUMO-C/ebpa fusion protein could rescue hematological defects in the dnmt1 mutants. Finally, dnmt1 and cebpa double null embryos exhibited no obvious abnormal hematopoiesis indicated that the HSPC defects triggered by dnmt1 mutation were C/ebpa dependent.
conclusionsDnmt1 is required for HSPC maintenance via cebpa regulation during definitive hematopoiesis in zebrafish.
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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.