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Chinese Academy of Sciences Institutional Repositories Grid
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
出版日期2011-10-28
卷号286期号:43页码:37196-37206
ISSN号0021-9258
DOI10.1074/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
出版者AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC
WOS记录号WOS:000296542400020
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
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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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