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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
Ning, Bo ; Liu, Gang ; Liu, Yuanyuan ; Su, Xiufen ; Anderson, Gregory J. ; Zheng, Xin ; Chang, Yanzhong ; Guo, Mingzhou ; Liu, Yuanfang ; Zhao, Yuliang ; Nie, Guangjun
刊名journal of biological chemistry
2011
关键词TRANSCRIPTION FACTOR GATA-1 ACUTE MYELOID-LEUKEMIA MYELODYSPLASTIC SYNDROMES DNA-METHYLATION TERMINAL DIFFERENTIATION ERYTHROLEUKEMIA-CELLS EPIGENETIC REGULATION ERYTHROID PRECURSORS TARGET GENES FACTOR EKLF
DOI10.1074/jbc.M111.258129
英文摘要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 in to the regulation of E-boxes and explain, at least in part, the increased erythroid response to 5-aza-CdR treatment.; Biochemistry & Molecular Biology; SCI(E); EI; 3; ARTICLE; 43; 37196-37206; 286
语种英语
内容类型期刊论文
源URL[http://ir.pku.edu.cn/handle/20.500.11897/313136]  
专题化学与分子工程学院
推荐引用方式
GB/T 7714
Ning, Bo,Liu, Gang,Liu, Yuanyuan,et al. 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[J]. journal of biological chemistry,2011.
APA Ning, Bo.,Liu, Gang.,Liu, Yuanyuan.,Su, Xiufen.,Anderson, Gregory J..,...&Nie, Guangjun.(2011).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.journal of biological chemistry.
MLA Ning, Bo,et al."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".journal of biological chemistry (2011).
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