Predictive base substitution rules that determine the binding and transcriptional specificity of Maf recognition elements
Predictive base substitution rules that determine the binding and transcriptional specificity of Maf recognition elements
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DOI：
10.1111/j.1365-2443.2006.00965.x
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发表时间：
2006-06-01
期刊：
影响因子：
2.1
通讯作者：
Yamamoto, Masayuki
中科院分区：
文献类型：
--
作者：
Yamamoto, Tae;Kyo, Motoki;Yamamoto, Masayuki
小Maf转录因子具有碱性区域亮氨酸拉链基序，通过该基序它们与CNC和Bach蛋白形成同源二聚体或异源二聚体。小Maf和CNC/Bach蛋白二聚体的不同组合结合到顺式作用DNA元件（统称为Maf识别元件（MARE））以激活或抑制转录。由于由功能定义的MARE通常与共有序列不同，我们推测MARE中的序列变异形成了选择性Maf：Maf或Maf：CNC二聚体结合的基础。为了验证这一假设，我们分析了结合的Maf含有二聚体的MARE的变体序列，使用细菌表达的MafG和Nrf 2蛋白和表面等离子体共振微阵列成像技术。我们发现MARE中的碱基替换实际上决定了它们对不同二聚体的结合偏好。事实上，我们能够将MARE分为五组：MafG同源二聚体定向的MARE（组I和II），矛盾MARE（组III），MafG：Nrf 2异源二聚体定向的MARE（组IV）和沉默MARE（组V）。因此，这项研究表明，一组明确的规则有关的顺式作用元件确定是否一个给定的MARE优先与MafG同源二聚体或与MafG：Nrf 2异源二聚体。
Small Maf transcription factors possess a basic region-leucine zipper motif through which they form homodimers or heterodimers with CNC and Bach proteins. Different combinations of small Maf and CNC/Bach protein dimers bind to cis-acting DNA elements, collectively referred to as Maf-recognition elements (MAREs), to either activate or repress transcription. As MAREs defined by function are often divergent from the consensus sequence, we speculated that sequence variations in the MAREs form the basis for selective Maf:Maf or Maf:CNC dimer binding. To test this hypothesis, we analyzed the binding of Maf-containing dimers to variant sequences of the MARE using bacterially expressed MafG and Nrf2 proteins and a surface plasmon resonance-microarray imaging technique. We found that base substitutions in the MAREs actually determined their binding preference for different dimers. In fact, we were able to categorize MAREs into five groups: MafG homodimer-orientd MAREs (Groups I and II), ambivalent MAREs (Group III), MafG:Nrf2 heterodimer-orientd MAREs (Group IV), and silent MAREs (Group V). This study thus manifests that a clear set of rules pertaining to the cis-acting element determine whether a given MARE preferentially associates with MafG homodimer or with MafG:Nrf2 heterodimer.