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首页> 外文期刊>Molecular and Cellular Biology >Multiple Functional Domains of AML1: PU.1 and C/EBPα Synergize with Different Regions of AML1
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Multiple Functional Domains of AML1: PU.1 and C/EBPα Synergize with Different Regions of AML1

机译：AML1的多个功能域：PU.1和C /EBPα与AML1的不同区域协同作用

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Control elements of many genes are regulated by multiple activators working in concert to confer the maximal level of expression, but the mechanism of such synergy is not completely understood. The promoter of the human macrophage colony-stimulating factor (M-CSF) receptor presents an excellent model with which we can study synergistic, tissue-specific activation for two reasons. First, myeloid-specific expression of the M-CSF receptor is regulated transcriptionally by three factors which are crucial for normal hematopoiesis: PU.1, AML1, and C/EBPα. Second, these proteins interact in such a way as to demonstrate at least two examples of synergistic activation. We have shown that AML1 and C/EBPα activate the M-CSF receptor promoter in a synergistic manner. As we report here, AML1 also synergizes, and interacts physically, with PU.1. Detailed analysis of the physical and functional interaction of AML1 with PU.1 and C/EBPα has revealed that the proteins contact one another through their DNA-binding domains and that AML1 exhibits cooperative DNA binding with C/EBPα but not with PU.1. This difference in DNA-binding abilities may explain, in part, the differences observed in synergistic activation. Furthermore, the activation domains of all three factors are required for synergistic activation, and the region of AML1 required for synergy with PU.1 is distinct from that required for synergy with C/EBPα. These observations present the possibility that synergistic activation is mediated by secondary proteins contacted through the activation domains of AML1, C/EBPα, and PU.1.
机译：许多基因的控制元件受多个激活因子共同调控以赋予其最大表达水平，但这种协同作用的机制尚不完全清楚。人类巨噬细胞集落刺激因子（M-CSF）受体的启动子提供了一个极好的模型，出于两个原因，我们可以使用该模型研究协同的组织特异性激活。首先，M-CSF受体的髓样特异性表达受三个对正常造血至关重要的因素转录调控：PU.1，AML1和C /EBPα。其次，这些蛋白质以证明至少两个协同激活实例的方式相互作用。我们已经显示，AML1和C /EBPα以协同方式激活M-CSF受体启动子。正如我们在此处报告的那样，AML1还与PU.1协同并在物理上进行交互。对AML1与PU.1和C /EBPα的物理和功能相互作用的详细分析表明，这些蛋白质通过其DNA结合结构域相互接触，并且AML1与C /EBPα而不是与PU.1表现出协同的DNA结合。 DNA结合能力的这种差异可能部分解释了协同激活中观察到的差异。此外，所有三个因子的激活域是协同激活所必需的，与PU.1协同作用所需的AML1区域与与C /EBPα协同作用所需的区域不同。这些观察结果表明协同激活可能由通过AML1，C /EBPα和PU.1的激活域接触的次级蛋白介导。

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