Co-operative DNA binding by GAGA transcription factor requires the conserved BTB/POZ domain and reorganizes promoter topology
Co-operative DNA binding by GAGA transcription factor requires the conserved BTB/POZ domain and reorganizes promoter topology
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DOI：
10.1093/emboj/18.3.698
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发表时间：
1999-02-01
期刊：
影响因子：
11.4
通讯作者：
Verrijzer, CP
中科院分区：
文献类型：
--
作者：
Katsani, KR;Hajibagheri, MAN;Verrijzer, CP
POZ结构域是一个保守的蛋白质-蛋白质相互作用基序，存在于多种参与发育、染色质重塑和人类癌症的转录因子中。在这里，我们研究GAGA转录因子的POZ结构域在启动子识别中的作用。GAGA的天然靶启动子通常含有多个GAGA结合元件。我们的研究结果表明，POZ结构域介导强合作结合多个网站，但抑制结合到单一网站。蛋白质交联和凝胶过滤色谱实验证实，POZ结构域是GAGA寡聚成更高级复合物所必需的。因此，GAGA寡聚化通过仅选择具有多个位点的启动子来增加结合特异性。电子显微镜显示，GAGA结合到多个网站作为一个大的寡聚体，并诱导弯曲的启动子DNA。我们的研究结果表明，一种新的模式的DNA结合GAGA，其中一个大的GAGA复合物结合多个GAGA元素，分布在一个区域的几百个碱基对。我们提出了一个模型，其中启动子DNA被包裹在一个GAGA多聚体的构象，可以排除正常的核小体形成。
The POZ domain is a conserved protein-protein interaction motif present in a variety of transcription factors involved in development, chromatin remodelling and human cancers, Here, we study the role of the POZ domain of the GAGA transcription factor in promoter recognition. Natural target promoters for GAGA typically contain multiple GAGA-binding elements. Our results show that the POZ domain mediates strong cooperative binding to multiple sites but inhibits binding to single sites. Protein cross-linking and gel filtration chromatography experiments established that the POZ domain is required for GAGA oligomerization into higher order complexes. Thus, GAGA oligomerization increases binding specificity by selecting only promoters with multiple sites. Electron microscopy revealed that GAGA binds to multiple sites as a large oligomer and induces bending of the promoter DNA. Our results indicate a novel mode of DNA binding by GAGA, in which a large GAGA complex binds multiple GAGA elements that are spread out over a region of a few hundred base pairs. We suggest a model in which the promoter DNA is wrapped around a GAGA multimer in a conformation that may exclude normal nucleosome formation.