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首页> 外文期刊>Proceedings of the National Academy of Sciences of the United States of America >Activator-Mediator binding regulates Mediator-cofactor interactions
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Activator-Mediator binding regulates Mediator-cofactor interactions

机译：激活剂-介体结合调节介体-辅因子相互作用

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摘要

The 26-subunit, 1.2 MDa human Mediator complex is essential for expression of perhaps all protein-coding genes. Activator binding triggers major structural shifts within Mediator, suggesting a straightforward means to spatially and temporally regulate Mediator activity. By using mass spectrometry (MudPIT) and other techniques, we have compared the subunit composition of Mediator in three different structural states: bound to the activator SREBP-1a, VP16, or an activator-free state. As expected, consensus Mediator subunits were similarly represented in each sample. However, we identify a set of cofactors that interact specifically with activator-bound but not activator-free Mediator, suggesting activator binding triggers new Mediator-cofactor interactions. Furthermore, MudPIT combined with biochemical assays reveals a nonoverlapping set of coregulatory factors associated with SREBP-Mediator vs. VP16-Mediator. These data define an expanded role for activators in regulating gene expression in humans and suggest that distinct, activator-induced structural shifts regulate Mediator function in gene-specific ways.
机译：26个亚基的1.2 MDa人类介体复合物对于可能表达所有蛋白质编码基因至关重要。激活剂结合触发介体内的主要结构变化，表明在空间和时间上调节介体活性的直接方法。通过使用质谱（MudPIT）和其他技术，我们比较了介体在三种不同结构状态下的亚基组成：与活化剂SREBP-1a，VP16或无活化剂结合。如预期的那样，每个样本中共有共识介体亚基。但是，我们确定了一组辅因子，这些辅因子与活化剂结合的但不与无活化剂的介体发生特异性相互作用，这表明活化剂结合会触发新的介体-辅因子相互作用。此外，MudPIT与生化分析相结合揭示了一组与SREBP-Mediator与VP16-Mediator相关的核心调节因子。这些数据定义了激活剂在调节人类基因表达中的扩展作用，并表明不同的，激活剂诱导的结构转变以基因特异性方式调节介体功能。

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