Structure and function of the upstream promotor of the human Mafbx gene: the proximal upstream promotor modulates tissue-specificity.
Structure and function of the upstream promotor of the human Mafbx gene: the proximal upstream promotor modulates tissue-specificity.
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人类 Mafbx 基因上游启动子的结构和功能:近端上游启动子调节组织特异性。
DOI:
10.1002/jcb.20468
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发表时间:
2005
影响因子:
4
通讯作者:
Cardozo,ChristopherP
中科院分区:
文献类型:
--
作者:
Zhao,Weidong;Wu,Yong;Zhao,Jingbo;Guo,Shuang;Bauman,WilliamA;Cardozo,ChristopherP
Muscle loss has been linked to increased expression of an ubiquitin ligase termed muscle atrophy F‐box (MAFbx), a nuclear protein involved in degradation of MyoD. To gain insights into mechanisms by which the humanMAFbxgene is controlled, the structure of its upstream promotor were studied, and its expression in cultured cells was characterized. Expression of MAFbx was found only in cells of muscle lineage. A reporter gene controlled by 948 bases of human MAFbx upstream promotor displayed similar cell‐type selectivity. MAFbx levels were greatly enhanced upon myogenic differentiation of C2C12 myoblasts, and differentiation markedly increased activity of a reporter gene constructed with 400 bp of upstream promotor from theMAFbxgene. The core promotor spanned approximately 160 bases beginning at −241 bp upstream of the first codon, included potential binding sites for MyoD and myogenin, and was highly conserved among mouse, rat, and humanMAFbxgenes. The major transcription start site for the humanMAFbxgene was 340 bases upstream of the ATG and was localized the highly conserved region of 140 bp. The findings indicate an important role for the immediate upstream promotor of the humanMAFbxgene in mediating its developmental expression and tissue specificity. © 2005 Wiley‐Liss, Inc.