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
文献类型:期刊论文
作者 | Ning, Bo1,6,7; Liu, Gang1,7; Liu, Yuanyuan2; Su, Xiufen2; Anderson, Gregory J.3; Zheng, Xin4; Chang, Yanzhong4; Guo, Mingzhou5; Liu, Yuanfang6; Zhao, Yuliang1 |
刊名 | Journal of biological chemistry
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出版日期 | 2011-10-28 |
卷号 | 286期号:43页码:37196-37206 |
ISSN号 | 0021-9258 |
DOI | 10.1074/jbc.m111.258129 |
通讯作者 | Nie, guangjun(niegj@nanoctr.cn) |
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. |
WOS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 |
WOS研究方向 | Biochemistry & Molecular Biology |
WOS类目 | Biochemistry & Molecular Biology |
语种 | 英语 |
WOS记录号 | WOS:000296542400020 |
出版者 | AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC |
URI标识 | http://www.irgrid.ac.cn/handle/1471x/2176032 |
专题 | 高能物理研究所 |
通讯作者 | Nie, Guangjun |
作者单位 | 1.Chinese Acad Sci, Key Lab Biol Effects Nanomat & Nanosafety, Natl Ctr Nanosci & Technol, Beijing 100190, Peoples R China 2.Jilin Univ, Affiliated Hosp 1, Changchun 130021, Jilin Province, Peoples R China 3.Queensland Inst Med Res, Iron Metab Lab, Brisbane, Qld 4092, Australia 4.Hebei Normal Univ, Coll Life Sci, Lab Mol Iron Metab, Shijiazhuang 050016, Hebei Province, Peoples R China 5.Chinese Peoples Liberat Army Gen Hosp, Dept Gastroenterol & Hepatol, Beijing 100853, Peoples R China 6.Peking Univ, Dept Chem Biol & Appl Chem, Coll Chem & Mol Engn, Beijing 100190, Peoples R China 7.Chinese Acad Sci, Grad Univ, Beijing 100049, Peoples R China |
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,2011,286(43):37196-37206. |
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,286(43),37196-37206. |
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 286.43(2011):37196-37206. |
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来源:高能物理研究所
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