RFX1, a single DNA-binding protein with a split dimerization domain, generates alternative complexes
RFX1, a single DNA-binding protein with a split dimerization domain, generates alternative complexes
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DOI：
10.1074/jbc.273.38.24504
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发表时间：
1998-09-18
影响因子：
4.8
通讯作者：
Shaul, Y
中科院分区：
文献类型：
--
作者：
Katan-Khaykovich, Y;Shaul, Y
各种病毒和细胞基因的转录受回文和非回文DNA位点的调节，这些位点类似于B型肝炎病毒增强子的EP元件，产生类似的DNA-蛋白质复合物。上EP复合物含有转录调节因子RFX 1的同源二聚体。我们发现，RFX 1具有分裂，扩展的二聚化结构域组成的几个进化上保守的盒子，其中一个先前被证明介导二聚化。这种异常长且复杂的二聚化结构域可以潜在地用于产生多个复合物。除了先前表征的复合物，RFX 1产生了一种新的DNA-蛋白质复合物，其迁移率极低，仅与回文DNA位点形成。二聚化结构域内的不同缺失改变了两种复合物的相对丰度，表明它们之间存在相互作用。低迁移率复合物的形成与转录抑制相关，因为这两种活性都是由保守区的几个部分介导的。我们的研究结果提出了一种机制，通过这种机制，扩展的二聚化结构域介导形成替代的同源二聚体复合物，这在亚基间相互作用的性质不同。通过参与不同类型的相互作用，该结构域可能会调节不同复合物的相对丰度，从而影响转录活性。
The transcription of various viral and cellular genes is regulated by palindromic and nonpalindromic DNA sites resembling the EP element of the hepatitis B virus enhancer, which generate similar DNA-protein complexes. The upper EP complex contains homodimers of the transcription regulator RFX1. We show that RFX1 possesses a split, extended dimerization domain composed of several evolutionarily conserved boxes, one of which was previously shown to mediate dimerization. Such an unusually long and complex dimerization domain could potentially serve for generating multiple complexes. In addition to the previously characterized complex, RFX1 generated a novel DNA-protein complex of extremely low mobility, formed only with palindromic DNA sites. Different deletions within the dimerization domain altered the relative abundance of the two complexes, suggesting an interplay between them. Formation of the low mobility complex correlated with transcriptional repression, in that both activities were mediated by several portions of the conserved region. Our results propose a mechanism by which the extended dimerization domain mediates the formation of alternative homodimeric complexes, which differ in the nature of the intersubunit interaction. By participating in different types of interactions, this domain may regulate the relative abundance of the different complexes, thus affecting transcriptional activity.