ArticleThe Journal of biological chemistry2011
5-aza-2'-deoxycytidine activates iron uptake and heme biosynthesis by increasing c-Myc nuclear localization and binding to the E-boxes of transferrin receptor 1 (TfR1) and ferrochelatase (Fech) genes.
Article in The Journal of biological chemistry, 2011. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 12 papers.
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Who cites it
12 citing papers in PubMed, 24 citations in OpenAlex.
- The novel role of DUSP4 in suppressing ferroptosis and promoting cytotoxicity of CD8British journal of cancer · 2025Article
- Eph receptor A4 regulates motor neuron ferroptosis in spinal cord ischemia/reperfusion injury in rats.Neural regeneration research · 2023Article
- Inhibition of lysyl oxidases synergizes with 5-azacytidine to restore erythropoiesis in myelodysplastic and myeloid malignancies.Nature communications · 2023Article
- Epigenetic modification regulates tumor progression and metastasis through EMT (Review).International journal of oncology · 2022Review
- Genome-wide variant-based study of genetic effects with the largest neuroanatomic coverage.BMC bioinformatics · 2021Article
- FAM210B is an erythropoietin target and regulates erythroid heme synthesis by controlling mitochondrial iron import and ferrochelatase activity.The Journal of biological chemistry · 2018Article
- Understanding the role of the chromosome 15q25.1 in COPD through epigenetics and transcriptomics.European journal of human genetics : EJHG · 2018Article
- MicroRNA-152-mediated dysregulation of hepatic transferrin receptor 1 in liver carcinogenesis.Oncotarget · 2016Article
- Targeting epigenetic regulations in cancer.Acta biochimica et biophysica Sinica · 2016Review
- The habenula and iron metabolism in cerebral mouse models of multiple sclerosis.Neuroscience letters · 2015Article
- Epigenetic therapy of cancer stem and progenitor cells by targeting DNA methylation machineries.World journal of stem cells · 2015Review
- Article
Corrections and comments
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Authors and funding
11 authors at 5 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
The hypomethylating agent 5-aza-2'-deoxycytidine (5-aza-CdR) and its derivatives have been successfully used for the treatment of myelodysplastic syndromes, and they frequently improve the anemia that usually accompanies these disorders. However, the molecular mechanisms underlying this action remain poorly understood. In this study, we used two erythroid models, murine erythroid leukemia cells and erythroid burst-forming unit-derived erythroblasts, to show that 5-aza-CdR induced erythroid differentiation and increased the expression of transferrin receptor 1 (TfR1) and ferrochelatase (Fech), thereby increasing iron uptake and heme biosynthesis. We have identified new regulatory E-boxes that lie outside of CpG islands in the TfR1 and Fech promoters, and the methylation status of these sites can be altered by 5-aza-CdR treatment. This in turn altered the binding of the transcription factor c-Myc to these promoter elements. Furthermore, 5-aza-CdR promoted the nuclear translocation of c-Myc and its binding to Max to form functional complexes. The coordinated actions of 5-aza-CdR on the methylation status of the target genes and in stimulating the nuclear translocation of c-Myc provide new molecular insights into the regulation of E-boxes and explain, at least in part, the increased erythroid response to 5-aza-CdR treatment.
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