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首页> 外文期刊>Molecular and Cellular Biology >Regulation of Transcription by Hypoxia Requires a Multiprotein Complex That Includes Hypoxia-Inducible Factor 1, an Adjacent Transcription Factor, and p300/CREB Binding Protein
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Regulation of Transcription by Hypoxia Requires a Multiprotein Complex That Includes Hypoxia-Inducible Factor 1, an Adjacent Transcription Factor, and p300/CREB Binding Protein

机译：缺氧对转录的调节需要多蛋白复合物，包括低氧诱导因子1，相邻的转录因子和p300 / CREB结合蛋白。

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摘要

Molecular adaptation to hypoxia depends on the binding of hypoxia-inducible factor 1 (HIF-1) to cognate response elements in oxygen-regulated genes. In addition, adjacent sequences are required for hypoxia-inducible transcription. To investigate the mechanism of interaction between these cis-acting sequences, the multiprotein complex binding to the lactate dehydrogenase A (LDH-A) promoter was characterized. The involvement of HIF-1, CREB-1/ATF-1, and p300/CREB binding protein (CBP) was demonstrated by techniques documenting in vitro binding, in combination with transient transfections that test the in vivo functional importance of each protein. In both the LDH-A promoter and the erythropoietin 3′ enhancer, formation of multiprotein complexes was analyzed by using biotinylated probes encompassing functionally critical cis-acting sequences. Strong binding of p300/CBP required interactions with multiple DNA binding proteins. Thus, the necessity of transcription factor binding sites adjacent to a HIF-1 site for hypoxically inducible transcription may be due to the requirement of p300 to interact with multiple transcription factors for high-affinity binding and activation of transcription. Since it has been found to interact with a wide range of transcription factors, p300 is likely to play a similar role in other genes, mediating interactions between DNA binding proteins, thereby activating stimulus-specific and tissue-specific gene transcription.
机译：分子对缺氧的适应性取决于缺氧诱导因子1（HIF-1）与氧调节基因中同源应答元件的结合。另外，缺氧诱导的转录需要相邻序列。为了研究这些 cis 作用序列之间的相互作用机理，表征了与乳酸脱氢酶A（LDH-A）启动子结合的多蛋白复合物。 HIF-1，CREB-1 / ATF-1和p300 / CREB结合蛋白（CBP）的参与已通过证明体外结合的技术与测试每种蛋白在体内功能重要性的瞬时转染相结合的方法得到证明。在LDH-A启动子和促红细胞生成素3'增强子中，通过使用包含功能关键的顺式作用序列的生物素化探针分析了多蛋白复合物的形成。 p300 / CBP的强结合需要与多种DNA结合蛋白相互作用。因此，与缺氧诱导转录的HIF-1位点相邻的转录因子结合位点的必要性可能是由于p300需要与多种转录因子相互作用以实现高亲和力结合和转录激活。由于已发现p300与多种转录因子相互作用，因此p300可能在其他基因中起类似的作用，介导DNA结合蛋白之间的相互作用，从而激活刺激特异性和组织特异性基因转录。

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