Study of the heme-binding factor Bach1 in heme responsive gene network

血红素及其降解产物对几乎所有形式的生命都是必不可少的。此外，血红素还通过与转录因子Bach1结合，起到细胞内基因表达调节的作用。Bach1与小分子MAF蛋白结合，与MAF识别元件(MARE)结合，调节血红素氧合酶-1和β-珠蛋白的表达。为了研究血红素应答基因网络在造血和氧化应激反应中的作用，我们使用了bach1缺陷小鼠，重点分析了造血。对小鼠外周血进行检测，未发现正常情况下有明显异常。α-珠蛋白、β-珠蛋白、P45、ALAsE基因的表达无明显差异。然而，当用苯肼诱导溶血性贫血时，与野生型小鼠相比，hach1^-lt；-/-&gt；突变体的β-珠蛋白基因表达略有降低，而血小板形成显著增加。这些发现提示Bach1可能在血小板的产生中发挥作用，作为转录抑制因子调节巨核细胞中依赖于mare的基因。我们还研究了Bach1在电离辐射反应中的作用。因为辐射经常会对细胞造成氧化损伤。与野生型小鼠相比，bach1基因缺陷小鼠的皮肤和小肠中的细胞凋亡在伽马照射后受到显著抑制。这一发现表明，Bach1可能参与了伽玛射线照射后应激反应的调节。

Heme and its degradation products are essential for practically all forms of life. Additionally, heme also functions as an intracellular regulator of gene expression by binding to Bach1, a transcription factor. Bach1 associates with small Maf proteins, bind to Maf recognition element (MARE) to regulate the expression of heme oxygenase-1 and β-globin. To study the network of heme responsive genes in hematopoiesis and oxidative stress response, we employed bach1-deficient mice, focusing on analysis of hematopoiesis. Upon examination of the peripheral blood of mice, we did not find any significant abnormality in normal condition. Also, no obvious difference was observed in expression of α-globin, β-globin mRNA, p45, ALAsE mRNA. However, when induced hemolytic anemia with phenylhydrazine, the hach1^<-/-> mutant showed slightly decreased expression of β-globin mRNA and significant increase of the platelet formation compared to wild-type mice. These findings suggest that Bach1 may play a role in platelet production, as a transcriptional repressor in the regulation of MARE-dependent genes in megakaryocytes.We also study a role of Bach1 in response to ionizing radiation. Since radiation often causes oxidative damage to cells. Apoptosis in skin and small intestine after gamma irradiation was significantly suppressed in bach1 deficient mice compared to wild-type mice. This finding suggests Bach1 could be involved in the regulation of stress response after gamma irradiation.