ZEB represses transcription through interaction with the corepressor CtBP
ZEB represses transcription through interaction with the corepressor CtBP
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DOI：
10.1073/pnas.96.12.6683
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发表时间：
1999-06-08
影响因子：
11.1
通讯作者：
Dean, DC
中科院分区：
文献类型：
--
作者：
Postigo, AA;Dean, DC
ZEB 是一种活性转录抑制因子，可调节脊椎动物的淋巴细胞和肌肉分化。它在果蝇中的同源物 (zfh-1) 对于体细胞和心肌的分化也是必需的。在这里，我们证明了 ZEE 和 zfh-1 与辅阻遏物 CtBP 相互作用来抑制转录。 ZEE 和 zfh-1 均在阻遏结构域的同一区域包含序列 PLDLS，并且我们证明该序列结合 CtBP-1 和 -2。在脊椎动物物种中，ZEE 包含两个额外的 CtBP 样结合位点（PLDLS 序列的变体），它们也结合 CtBP 蛋白，并且是完全阻遏蛋白活性所必需的。这三个位点具有累加效应，并且所有三个位点的突变对于消除与 CtBP 的结合和阻遏蛋白活性是必要的。最后，我们证明 CtBP 与 ZEE 在启动子处的相互作用对于阻遏蛋白活性是必要的。
ZEB is an active transcriptional repressor that regulates lymphocyte and muscle differentiation in vertebrates. its homologue in Drosophila (zfh-1) is also essential for differentiation of somatic and cardiac muscle. Here, we demonstrate that ZEE and zfh-1 interact with the corepressor CtBP to repress transcription. ZEE and zfh-1,both contain the sequence PLDLS in the same region of the repressor domain, and we demonstrate that this sequence binds CtBP-1 and -2. In vertebrate species, ZEE contains two additional CtBP-like binding sites (variations of the PLDLS sequence) that also bind CtBP proteins and are required for full repressor activity, The three sites have an additive effect, and mutation of all three sites is necessary to abolish both binding to CtBP and repressor activity. Finally, we demonstrate that the interaction of CtBP with ZEE at the promoter is necessary for repressor activity.