ArticleThe Journal of experimental medicine2021
DNMT3A haploinsufficiency causes dichotomous DNA methylation defects at enhancers in mature human immune cells.
Article in The Journal of experimental medicine, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 18 papers.
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Who cites it
18 citing papers in PubMed, 24 citations in OpenAlex.
- Clonal hematopoiesis-associated DNMT3A mutations derepress bivalent Polycomb target genes and enhance macrophage migration.bioRxiv : the preprint server for biology · 2026Article
- Clonal Hematopoiesis in Colorectal Cancer: Mechanisms and Implications.Cancer medicine · 2026Review
- Profiling active RNA polymerase II transcription start sites from total RNA by capped small RNA sequencing (csRNA-seq).Nature protocols · 2026Review
- Convergent DNA methylation abnormalities at enhancers and bivalent promoters in human growth disorders.Epigenetics & chromatin · 2025Article
- Understanding Human Oncogene Function and Cooperativity in Myeloid Malignancy Using iPSCs.Experimental hematology · 2025Review
- Efficient small fragment sequencing of human, cattle, and bison miRNA, small RNA, or csRNA-seq libraries using AVITI.BMC genomics · 2024Article
- Nascent transcription reveals regulatory changes in extremophile fishes inhabiting hydrogen sulfide-rich environments.Proceedings. Biological sciences · 2024Article
- Hematopoietic-specific heterozygous loss of Dnmt3a exacerbates colitis-associated colon cancer.The Journal of experimental medicine · 2023Article
- Enhancers associated with unstable RNAs are rare in plants.bioRxiv : the preprint server for biology · 2023Article
- Successful azacitidine therapy for myelodysplastic syndrome associated with VEXAS syndrome.International journal of hematology · 2023Article
- Article
- Constitutive loss of DNMT3A causes morbid obesity through misregulation of adipogenesis.eLife · 2022Article
- Decoding Transcription Regulatory Mechanisms Associated withmSystems · 2022Article
- DNMT3A Harboring Leukemia-Associated Mutations Directs Sensitivity to DNA Damage at Replication Forks.Clinical cancer research : an official journal of the American Association for Cancer Research · 2022Article
- Clonal hematopoiesis in cardiovascular disease and therapeutic implications.Nature cardiovascular research · 2022Article
- Glucocorticoid Receptor-Regulated Enhancers Play a Central Role in the Gene Regulatory Networks Underlying Drug Addiction.Frontiers in neuroscience · 2022Article
- Azacytidine Treatment for VEXAS Syndrome.HemaSphere · 2021Article
- Castleman disease.Nature reviews. Disease primers · 2021Review
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Authors and funding
14 authors at 4 institutions in 1 country.
Funding
Abstract
DNMT3A encodes an enzyme that carries out de novo DNA methylation, which is essential for the acquisition of cellular identity and specialized functions during cellular differentiation. DNMT3A is the most frequently mutated gene in age-related clonal hematopoiesis. As such, mature immune cells harboring DNMT3A mutations can be readily detected in elderly persons. Most DNMT3A mutations associated with clonal hematopoiesis are heterozygous and predicted to cause loss of function, indicating that haploinsufficiency is the predominant pathogenic mechanism. Yet, the impact of DNMT3A haploinsufficiency on the function of mature immune cells is poorly understood. Here, we demonstrate that DNMT3A haploinsufficiency impairs the gain of DNA methylation at decommissioned enhancers, while simultaneously and unexpectedly impairing DNA demethylation of newly activated enhancers in mature human myeloid cells. The DNA methylation defects alter the activity of affected enhancers, leading to abnormal gene expression and impaired immune response. These findings provide insights into the mechanism of immune dysfunction associated with clonal hematopoiesis and acquired DNMT3A mutations.
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