ArticleThe Journal of biological chemistry2014
3-Deazaneplanocin A (DZNep), an inhibitor of S-adenosylmethionine-dependent methyltransferase, promotes erythroid differentiation.
Article in The Journal of biological chemistry, 2014. 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, 50 citations in OpenAlex.
- Post-translational Modifications in Proteins: Prediction Methods, Biological Functions, and Diseases.MedComm · 2026Review
- Exploring the role of EZH2 in neuroinflammation: implications for innovative therapeutic strategies.Naunyn-Schmiedeberg's archives of pharmacology · 2026Review
- Review
- Targeting of Calbindin 1 rescues erythropoiesis in a human model of Diamond Blackfan anemia.Blood cells, molecules & diseases · 2023Article
- The Interplay between Dysregulated Metabolism and Epigenetics in Cancer.Biomolecules · 2023Review
- Elucidation of the Role of FAM210B in Mitochondrial Metabolism and Erythropoiesis.Molecular and cellular biology · 2022Article
- Interplay between cofactors and transcription factors in hematopoiesis and hematological malignancies.Signal transduction and targeted therapy · 2021Review
- Article
- EZH2 as a Potential Target for NAFLD Therapy.International journal of molecular sciences · 2020Review
- Embryonic erythropoiesis and hemoglobin switching require transcriptional repressor ETO2 to modulate chromatin organization.Nucleic acids research · 2020Article
- Differential expression of microRNA, miR-150 and enhancer of zeste homolog 2 (EZH2) in peripheral blood cells as early prognostic markers of severe forms of dengue.Journal of biomedical science · 2020Article
- PTEN Methylation by NSD2 Controls Cellular Sensitivity to DNA Damage.Cancer discovery · 2019Article
- Targeting EZH2 histone methyltransferase activity alleviates experimental intestinal inflammation.Nature communications · 2019Article
- Generation and Molecular Characterization of Human Ring Sideroblasts: a Key Role of Ferrous Iron in Terminal Erythroid Differentiation and Ring Sideroblast Formation.Molecular and cellular biology · 2019Article
- Targeting the MTF2-MDM2 Axis Sensitizes Refractory Acute Myeloid Leukemia to Chemotherapy.Cancer discovery · 2018Article
- Infection perturbs Bach2- and Bach1-dependent erythroid lineage 'choice' to cause anemia.Nature immunology · 2018Article
- The synthetic histone-binding regulator protein PcTF activates interferon genes in breast cancer cells.BMC systems biology · 2018Article
- Depletion of DNMT1 in differentiated human cells highlights key classes of sensitive genes and an interplay with polycomb repression.Epigenetics & chromatin · 2018Article
- Genome-wide analysis revealed that DZNep reduces tubulointerstitial fibrosis via down-regulation of pro-fibrotic genes.Scientific reports · 2018Article
- Dynamics of absorption, metabolism, and excretion of 5-aminolevulinic acid in human intestinal Caco-2 cells.Biochemistry and biophysics reports · 2017Article
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Authors and funding
11 authors at 2 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
EZH2, a core component of polycomb repressive complex 2 (PRC2), plays a role in transcriptional repression through histone H3 Lys-27 trimethylation and is involved in various biological processes, including hematopoiesis. It is well known that 3-deazaneplanocin A (DZNep), an inhibitor of S-adenosylmethionine-dependent methyltransferase that targets the degradation of EZH2, preferentially induces apoptosis in various hematological malignancies, suggesting that EZH2 may be a new target for epigenetic treatment. Because PRC2 participates in epigenetic silencing of a subset of GATA-1 target genes during erythroid differentiation, inhibition of EZH2 may influence erythropoiesis. To explore this possibility, we evaluated the impact of DZNep on erythropoiesis. DZNep treatment significantly induced erythroid differentiation of K562 cells, as assessed by benzidine staining and quantitative RT-PCR analysis for representative erythroid-related genes, including globins. When we evaluated the effects of DZNep in human primary erythroblasts derived from cord blood CD34-positive cells, the treatment significantly induced erythroid-related genes, as observed in K562 cells, suggesting that DZNep induces erythroid differentiation. Unexpectedly, siRNA-mediated EZH2 knockdown had no significant effect on the expression of erythroid-related genes. Transcriptional profiling of DZNep-treated K562 cells revealed marked up-regulation of SLC4A1 and EPB42, previously reported as representative targets of the transcriptional corepressor ETO2. In addition, DZNep treatment reduced the protein level of ETO2. These data suggest that erythroid differentiation by DZNep may not be directly related to EZH2 inhibition but may be partly associated with reduced protein level of hematopoietic corepressor ETO2. These data provide a better understanding of the mechanism of action of DZNep, which may be exploited for therapeutic applications for hematological diseases, including anemia.
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