Activation of wingless targets requires bipartite recognition of DNA by TCF.
Activation of wingless targets requires bipartite recognition of DNA by TCF.
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DOI：
10.1016/j.cub.2008.10.047
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发表时间：
2008-12-09
期刊：
影响因子：
--
通讯作者：
Cadigan KM
中科院分区：
文献类型：
--
作者：
Chang MV;Chang JL;Gangopadhyay A;Shearer A;Cadigan KM
转录因子对DNA的特异性识别对于精确的基因调控是必不可少的。在果蝇的无翅（Wg）信号转导中，靶基因的调控由TCF控制，TCF通过HMG结构域与特定的DNA序列结合。然而，在构成TCF结合位点的物质中存在相当大的简并性，这提高了它不足以用于靶定位的可能性。人TCF的一些同种型含有称为C-钳的结构域，其在体外介导与延伸序列的结合。然而，这一延伸序列对Wnt反应元件（WRE）功能的意义尚不清楚。在这份报告中，我们确定了一个新的顺式调控元件命名的TCF辅助网站（辅助网站），是必不可少的激活几个WRE。该基序极大地增强了TCF结合位点响应Wg信号传导的能力。果蝇TCF含有一个C-钳，增强体外结合TCF辅助位点对，是转录激活WRE含有辅助位点所必需的。对TCF和辅助位点簇的全基因组搜索确定了两个新的WRE。我们的数据表明，DNA识别苍蝇TCF发生通过一个双向机制，涉及HMG结构域和C-钳，这使得TCF定位和激活WREs在细胞核中。
Specific recognition of DNA by transcription factors is essential for precise gene regulation. In Wingless (Wg) signaling in Drosophila, target gene regulation is controlled by TCF, which binds to specific DNA sequences through a HMG domain. However, there is considerable degeneracy in what constitutes a TCF binding site, raising the possibility that it is not sufficient for target location. Some isoforms of human TCF contain a domain termed the C-clamp that mediates binding to an extended sequence in vitro. However, the significance of this extended sequence for the function of Wnt response elements (WREs) is unclear. In this report, we identified a new cis-regulatory element named the TCF Helper site (Helper site) that is essential for activation of several WREs. This motif greatly augments the ability of TCF binding sites to respond to Wg signaling. Drosophila TCF contains a C-clamp that enhances in vitro binding to TCF-Helper site pairs and is required for transcriptional activation of WREs containing Helper sites. A genome-wide search for clusters of TCF and Helper sites identified two new WREs. Our data suggest that DNA recognition by fly TCF occurs through a bipartite mechanism involving both the HMG domain and C-clamp, which enables TCF to locate and activate WREs in the nucleus.
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