ArticleThe Journal of biological chemistry2012
Deficiency of H3K79 histone methyltransferase Dot1-like protein (DOT1L) inhibits cell proliferation.
Article in The Journal of biological chemistry, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 84 papers.
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Who cites it
84 citing papers in PubMed, 142 citations in OpenAlex.
- Epigenetics in lung cancer precision medicine: from bench to bedside-a narrative review.Translational lung cancer research · 2026Review
- Histone methyltransferase DOT1L differentially affects the development of dendritic cell subsets.Life science alliance · 2026Article
- Neointimal hyperplasia and vascular restenosis: from molecular mechanisms to therapeutic interventions.Molecular biomedicine · 2026Review
- Targeting senescence-associated secretory phenotype macrophage: apigenin inhibits DOT1L-dependent H3K79me2 atFrontiers in molecular biosciences · 2026Article
- Effects of aging and anti-aging dietary restriction on regulators of the [NADPH]/[NADPFree radical biology & medicine · 2025Review
- DOT1L as a Therapeutic Target: Insights into Epigenetic Regulation and Cancer Treatment.Biomolecules & therapeutics · 2025Review
- Unveiling the Role of Histone Methyltransferases in Psoriasis Pathogenesis: Insights from Transcriptomic Analysis.International journal of molecular sciences · 2025Article
- DOT1L Mediates Stem Cell Maintenance and Represents a Therapeutic Vulnerability in Cancer.Cancer research · 2025Review
- Histone methylation modification and diabetic kidney disease: Potential molecular mechanisms and therapeutic approaches (Review).International journal of molecular medicine · 2024Review
- Dexamethasone Inhibits the Growth of B-Lymphoma Cells by Downregulating DOT1L.Cancer reports (Hoboken, N.J.) · 2024Article
- Discovery of first-in-class DOT1L inhibitors against the R231Q gain-of-function mutation in the catalytic domain with therapeutic potential of lung cancer.Acta pharmaceutica Sinica. B · 2024Article
- β-hydroxybutyrate resensitizes colorectal cancer cells to oxaliplatin by suppressing H3K79 methylation in vitro and in vivo.Molecular medicine (Cambridge, Mass.) · 2024Article
- TNFα Induces DNA and Histone Hypomethylation and Pulmonary Artery Smooth Muscle Cell Proliferation Partly via Excessive Superoxide Formation.Antioxidants (Basel, Switzerland) · 2024Article
- An emerging maestro of immune regulation: how DOT1L orchestrates the harmonies of the immune system.Frontiers in immunology · 2024Review
- Tumor-suppressive functions of protein lysine methyltransferases.Experimental & molecular medicine · 2023Review
- Rare de novo gain-of-function missense variants in DOT1L are associated with developmental delay and congenital anomalies.American journal of human genetics · 2023Article
- Predictive value of DOT1L mutations for clinical outcomes in non-small-cell lung cancer patients receiving immune checkpoint inhibitor therapy.Clinical and translational medicine · 2023Article
- Gain-of-function mutations in the catalytic domain ofScience advances · 2023Article
- A novel role of DOT1L in kidney diseases.Molecular biology reports · 2023Review
- CRISPR-Cas9-mediated gene therapy in lung cancer.Clinical & translational oncology : official publication of the Federation of Spanish Oncology Societies and of the National Cancer Institute of Mexico · 2023Review
24 more citing papers are in PubMed but not listed here.
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
5 authors at 2 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Dot1-like protein (DOT1L) is an evolutionarily conserved histone methyltransferase that methylates lysine 79 of histone H3 (H3K79). Mammalian DOT1L participates in the regulation of transcription, development, erythropoiesis, differentiation, and proliferation of normal cells. However, the role of DOT1L in cancer cell proliferation has not been fully elucidated. DOT1L siRNA-transfected A549 or NCI-H1299 lung cancer cells displayed a nonproliferating multinucleated phenotype. DOT1L-deficient cells also showed abnormal mitotic spindle formation and centrosome number, suggesting that DOT1L deficiency leads to chromosomal missegregation. This chromosomal instability in DOT1L-deficient cells led to cell cycle arrest at the G(1) phase and induced senescence as determined by enhanced activity of senescence-associated β-galactosidase activity. Meanwhile, overexpression of a catalytically active DOT1L, not an inactive mutant, restored DOT1L siRNA-induced phenotypes. Overall, these data imply that down-regulation of DOT1L-mediated H3K79 methylation disturbs proliferation of human cells. In addition, although H3K79 methylation is down-regulated in aged tissues, it is up-regulated in lung cancer cell lines and tumor tissues of lung cancer patients. Therefore, H3K79 methylation is a critical histone modification that regulates cell proliferation and would be a novel histone mark for aging and cancer.
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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.