DISTINCT TPR MOTIFS OF CYC8 ARE INVOLVED IN RECRUITING THE CYC8-TUP1 COREPRESSOR COMPLEX TO DIFFERENTIALLY REGULATE PROMOTERS
DISTINCT TPR MOTIFS OF CYC8 ARE INVOLVED IN RECRUITING THE CYC8-TUP1 COREPRESSOR COMPLEX TO DIFFERENTIALLY REGULATE PROMOTERS
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DOI：
10.1101/gad.9.7.821
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发表时间：
1995-04-01
影响因子：
10.5
通讯作者：
STRUHL, K
中科院分区：
文献类型：
--
作者：
TZAMARIAS, D;STRUHL, K
酵母Cyc8(Ssn6)-Tup1复合体是受葡萄糖、氧气、细胞类型和DNA损伤调节的不同基因组转录抑制所必需的。已经提出Cyc8-Tup1复合物是一种通过与通路特异性dna结合蛋白相互作用而招募到启动子的辅抑制因子。之前，我们发现Tup1的一个特定区域介导了该复合体的一般转录抑制功能。在这里，我们定义了Cyc8的功能域，Cyc8是一种主要由TPR基序的10个串联拷贝组成的蛋白质。TPR基序的不同组合需要与Tup1直接相互作用，抑制氧调节基因，抑制葡萄糖调节基因。相比之下，Tup1的WD基序对于葡萄糖和氧气调节的基因的抑制不是必需的，但它们对于细胞类型和DNA损伤调节的基因是必需的。此外，我们发现Cyc8-Tup1复合物同时作为Mig1的辅助抑制因子和抑制剂，Mig1是一种结合葡萄糖抑制基因启动子的蛋白质。这些观察结果表明，不同的Cyc8 TPR基序和Tup1 WD结构域介导不同的蛋白-蛋白相互作用，这些相互作用将Cyc8-Tup1协同抑制因子与通路特异性调控所需的结构不同的dna结合蛋白联系起来。
The yeast Cyc8(Ssn6)-Tup1 complex is required for transcriptional repression of distinct sets of genes that are regulated by glucose, oxygen, cell type, and DNA damage. It has been proposed that the Cyc8-Tup1 complex is a corepressor that is recruited to promoters by interacting with pathway-specific DNA-binding proteins. Previously, we showed that a specific region of Tup1 mediates the general transcriptional repression function of the complex. Here, we define functional domains of Cyc8, a protein consisting primarily of 10 tandem copies of a TPR motif. Distinct combinations of TPR motifs are required specifically for direct interaction with Tup1, repression of oxygen-regulated genes, and repression of glucose-regulated genes. In contrast, the WD motifs of Tup1 are not essential for repression of genes regulated by glucose and oxygen, but they are required for those regulated by cell type and DNA damage. In addition, we show that the Cyc8-Tup1 complex functions both as a corepressor and an inhibitor of Mig1, a protein that binds to promoters of glucose-repressible genes. These observations suggest that different Cyc8 TPR motifs and the Tup1 WD domain mediate distinct protein-protein interactions that link the Cyc8-Tup1 corepressor to structurally dissimilar DNA-binding proteins required for pathway-specific regulation.