DNA recognition mechanism of the ONECUT homeodomain of transcription factor HNF-6
DNA recognition mechanism of the ONECUT homeodomain of transcription factor HNF-6
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DOI：
10.1016/j.str.2006.11.004
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发表时间：
2007-01-01
期刊：
影响因子：
5.7
通讯作者：
Tanaka, Isao
中科院分区：
文献类型：
--
作者：
Iyaguchi, Daisuke;Yao, Min;Tanaka, Isao
肝细胞核因子-6（HNF-6）是一种肝脏富集的转录因子，控制各种组织（如胰腺和肝脏）的发育，并调节几种肝脏基因的表达。该蛋白属于ONECUT类同源结构域蛋白，并且含有由单个切割结构域和特征性同源结构域组成的二分DNA结合结构域。该转录因子具有两种不同的DNA结合和转录激活模式，其根据靶基因使用不同的共激活因子。与TTR启动子的HNF-6结合位点复合的HNF-6 α的二分DNA结合结构域的晶体结构揭示了该蛋白的DNA识别机制。比较我们的结构与DNA的HNF-6或Oct-1的结构，我们讨论了与DNA结合和这种蛋白质的双重作用模式的结构基础相关的特征，我们提出了一种策略的可变性的靶基因的转录激活。
Hepatocyte nuclear factor-6 (HNF-6), a liver-enriched transcription factor, controls the development of various tissues, such as the pancreas and liver, and regulates the expression of several hepatic genes. This protein belongs to the ONECUT class of homeodomain proteins and contains a bipartite DNA-binding domain composed of a single cut domain and a characteristic homeodomain. This transcription factor has two distinct modes of DNA binding and transcriptional activation that use different coactivators depending on the target gene. The crystal structure of the bipartite DNA-binding domain of HNF-6 alpha complexed with the HNF-6-binding site of the TTR promoter revealed the DNA recognition mechanism of this protein. Comparing our structure with the DNA-free structure of HNF-6 or the structure of Oct-1, we discuss characteristic features associated with DNA binding and the structural basis for the dual mode of action of this protein, and we suggest a strategy for variability of transcriptional activation of the target gene.