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

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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.