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首页> 外文期刊>Proceedings of the National Academy of Sciences of the United States of America >Heme regulates the dynamic exchange of Bach1 and NF-E2-related factors in the Maf transcription factor network
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Heme regulates the dynamic exchange of Bach1 and NF-E2-related factors in the Maf transcription factor network

机译：血红素调节Maf转录因子网络中Bach1和NF-E2相关因子的动态交换

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摘要

Small Maf proteins serve as dual-function transcription factors through an exchange of their heterodimerization partners. For example, as heterodimers with hematopoietic cell-specific p45 NF-E2 or NF-E2-related factors (Nrf), they activate the β-globin or antioxidative stress enzyme heme oxygenase 1 (HO-1) genes, respectively. In contrast, together with Bachl, they repress these same genes. However, the signals leading to this partner exchange are not known. Using chromatin immunoprecipitation assays in NIH 3T3 cells, we show that heme, an inducer of ho-1, promotes displacement of Bachl from the MafK-occupied ho-1 enhancers, which is followed by Nrf2 binding to these elements. Whereas histone H3 at the ho-1 enhancers and promoter is hyperacetylated irrespective of gene activity, exposure of cells to heme results in de novo hyperacetylation and hypermethylation of histone H3 in the transcribed region. These data indicate that, under normal conditions, the chromatin structure of ho-1 is in a preactivation state, but transcription is repressed by Bach1. Heme induces switching of Maf dimers, resulting in ho-1 expression. Heme also promotes displacement of Bach1 from the β-globin locus control region without affecting MafK binding in murine erythroleukemia cells. Thus, heme functions as a signaling molecule for gene expression in higher eukaryotes.
机译：小黑手党蛋白通过交换其异二聚体伴侣而充当双重功能转录因子。例如，作为具有造血细胞特异性p45 NF-E2或NF-E2相关因子（Nrf）的异二聚体，它们分别激活β-珠蛋白或抗氧化应激酶血红素加氧酶1（HO-1）基因。相反，它们与Bachl一起抑制这些相同的基因。但是，导致此伙伴交换的信号未知。使用NIH 3T3细胞中的染色质免疫沉淀测定法，我们显示了血红素（ho-1的诱导剂）可促进Bachl从MafK占据的ho-1增强剂中置换，随后Nrf2与这些元素结合。尽管ho-1增强子和启动子处的组蛋白H3均被过度乙酰化，而与基因活性无关，但细胞暴露于血红素会导致转录区中组蛋白H3从头过度乙酰化和甲基化。这些数据表明，在正常条件下，ho-1的染色质结构处于预激活状态，但转录受到Bach1的抑制。血红素诱导Maf二聚体的转换，导致ho-1表达。血红素还促进Bach1从β珠蛋白基因座控制区的置换，而不影响鼠红白血病细胞中的MafK结合。因此，血红素在高级真核生物中充当基因表达的信号分子。

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