Bach1 repression of ferritin and thioredoxin reductase1 is heme-sensitive in cells and in vitro and coordinates expression with heme oxygenase1, β-globin, and NADP(H) quinone (oxido) reductase1
Bach1 repression of ferritin and thioredoxin reductase1 is heme-sensitive in cells and in vitro and coordinates expression with heme oxygenase1, β-globin, and NADP(H) quinone (oxido) reductase1
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DOI：
10.1074/jbc.m700254200
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发表时间：
2007-11-23
影响因子：
4.8
通讯作者：
Theil, Elizabeth C.
中科院分区：
文献类型：
--
作者：
Hintze, Korry J.;Katoh, Yasutake;Theil, Elizabeth C.
铁蛋白基因转录受血红素调节，铁蛋白mRNA翻译也受血红素调节，铁蛋白mRNA翻译由研究充分的mRNA.IRE/IRP蛋白复合物介导。铁蛋白基因中的血红素敏感DNA序列是存在于由血红素诱导并由Bach 1抑制的其他几个基因中的maf识别/抗氧化反应元件。我们现在报告，染色质免疫沉淀巴赫1抗血清含有铁蛋白DNA序列。此外，转染细胞中Bach 1蛋白的过表达降低了铁蛋白表达，表明内源性Bach 1不足以完全抑制;用反义RNA降低Bach 1增加了铁蛋白表达。硫氧还蛋白还原酶1（也含有maf识别/抗氧化反应元件但研究较少的基因）对铁蛋白的反应类似，阳性对照血红素加氧酶1和NADP（H）醌（氧化）还原酶1也是如此。细胞中的Bach 1-DNA启动子相互作用在体外用可溶性重组Bach 1蛋白证实，并揭示了Bach 1/DNA稳定性的定量范围：铁蛋白L类似于铁蛋白H类似于β-珠蛋白，β-珠蛋白类似于2倍>血红素加氧酶1 =醌还原酶β-珠蛋白类似于4倍>硫氧还蛋白还原酶1。这样的结果表明，细胞Bach 1浓度的调制的可能性，将有不同的影响之间的基因协调调节的MAF识别/抗氧化剂响应元素在铁/氧/抗氧化剂代谢。
Ferritin gene transcription is regulated by heme as is ferritin mRNA translation, which is mediated by the well studied mRNA.IRE/IRP protein complex. The heme-sensitive DNA sequence in ferritin genes is the maf recognition/antioxidant response element present in several other genes that are induced by heme and repressed by Bach1. We now report that chromatin immunoprecipitated with Bach1 antiserum contains ferritin DNA sequences. In addition, overexpression of Bach1 protein in the transfected cells decreased ferritin expression, indicating insufficient endogenous Bach1 for full repression; decreasing Bach1 with antisense RNA increased ferritin expression. Thioredoxin reductase1, a gene that also contains a maf recognition/antioxidant response element but is less studied, responded similarly to ferritin, as did the positive controls heme oxygenase1 and NADP(H) quinone (oxido) reductase1. Bach1-DNA promoter interactions in cells were confirmed in vitro with soluble, recombinant Bach1 protein and revealed a quantitative range of Bach1/DNA stabilities: ferritin L similar to ferritin H similar to beta-globin, beta-globin similar to 2-fold > heme oxygenase1 = quinone reductase beta-globin similar to 4-fold > thioredoxin reductase1. Such results indicate the possibility that modulation of cellular Bach1 concentrations will have variable effects among the genes coordinately regulated by maf recognition/ antioxidant response elements in iron/oxygen/antioxidant metabolism.