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，作为细胞内基因表达的调节因子。Bach1与Maf小蛋白结合，结合Maf识别元件（MARE）调控血红素加氧酶-1和β-珠蛋白的表达。为了研究造血和氧化应激反应中血红素反应基因的网络，我们采用bach1缺陷小鼠，重点分析造血。对小鼠外周血进行检查，正常情况下未见明显异常。α-珠蛋白、β-珠蛋白mRNA、p45、ALAsE mRNA的表达差异无统计学意义。然而，当苯肼诱导溶血性贫血时，hach1^<-/->突变体与野生型小鼠相比，β-珠蛋白mRNA的表达略有下降，血小板形成明显增加。这些发现表明Bach1可能在血小板产生中发挥作用，作为巨核细胞中mare依赖基因的转录抑制因子。我们还研究了Bach1在电离辐射响应中的作用。因为辐射通常会对细胞造成氧化损伤。与野生型小鼠相比，γ辐照后bach1缺陷小鼠皮肤和小肠的细胞凋亡明显受到抑制。这一发现提示Bach1可能参与γ辐照后应激反应的调节。

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.