Transcriptional repression activity of PAX3 is modulated by competition between corepressor KAP1 and heterochromatin protein 1
Transcriptional repression activity of PAX3 is modulated by competition between corepressor KAP1 and heterochromatin protein 1
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DOI：
10.1016/j.bbrc.2006.08.064
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发表时间：
2006-10-20
影响因子：
3.1
通讯作者：
Yang, Wen-Ming
中科院分区：
文献类型：
--
作者：
Hsieh, Mei-Ju;Yao, Ya-Li;Yang, Wen-Ming
Pax 3是一种对正常发育和肿瘤发生至关重要的转录因子。已知Pax 3可引起Waardenburg综合征和小儿腺泡状横纹肌肉瘤，但Pax 3如何调节转录尚不清楚。在这里，我们报告说，Pax 3抑制转录和选择性地与异染色质蛋白1（HP 1）和KAP 1相互作用。KAP 1作为转录辅阻遏物通过募集HP 1来促进通过组蛋白去乙酰化和甲基化形成封闭的染色质。我们发现KAP 1是Pax 3的辅阻遏物，通过增强Pax 3的抑制活性。出乎意料的是，HP 1 γ减弱了Pax 3的抑制活性。在靶启动子上，KAP 1和HP 1 γ竞争与N-末端配对结构域上的Pax 3结合，并且Pax 3的C-末端结构域控制Pax 3的亚细胞定位。两者合计，我们的研究结果表明，Pax 3抑制转录通过一种新的机制，涉及竞争辅阻遏KAP 1和异染色质结合蛋白HP 1 γ之间。(c)2006年爱思唯尔公司All rights reserved.
Pax3 is a transcription factor crucial for normal development and tumorigenesis. Pax3 has been known to cause Waardenburg syndrome and pediatric alveolar rhabdomyosarcoma, but how Pax3 regulates transcription is not clear. Here, we report that Pax3 represses transcription and selectively interacts with heterochromatin protein 1 (HP1) and KAP1. KAP1 functions as a transcriptional corepressor by recruiting HP1 to facilitate the formation of a closed chromatin through histone deacetylation and methylation. We found that KAP1 is a corepressor for Pax3 by augmenting the repressional activity of Pax3. Unexpectedly, HP1 gamma diminishes the repressional activity of Pax3. On target promoters, KAP1 and HP1 gamma compete for binding with Pax3 on the N-terminal paired domain, and the C-terminal domain of Pax3 governs the subcellular localization of Pax3. Taken together, our results indicate that Pax3 represses transcription through a novel mechanism involving competition between corepressor KAP1 and the heterochromatin-binding protein HP1 gamma. (c) 2006 Elsevier Inc. All rights reserved.