Transactivation mechanisms of mouse clock transcription factors, mClock and mArnt3
Transactivation mechanisms of mouse clock transcription factors, mClock and mArnt3
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DOI：
10.1046/j.1365-2443.2000.00363.x
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发表时间：
2000-09-01
期刊：
影响因子：
2.1
通讯作者：
Fujii-Kuriyama, Y
中科院分区：
文献类型：
--
作者：
Takahata, S;Ozaki, T;Fujii-Kuriyama, Y
背景：Arnt3（也称为BMAL1或MOP3）/Clock异源二聚体是昼夜节律的积极调节因子，可激活per1和抗利尿激素等靶基因的转录。结果：研究了mArnt3/mClock异源二聚体的转录机制。mClock不具有任何明显的激活结构域，而mArnt3在最c端含有一个转录激活结构域，即使在一个杂交系统中，其活性也不表达，直到它与mClock结合。有研究表明，mClock在发挥mArnt3/mClock异源二聚体的转录增强作用中起着调节或结构作用。mClock的559-492氨基酸的缺失显著降低了mArnt3/mClock异源二聚体的反激活活性，这与Clock-Delta 19突变体的结果一致。酵母和哺乳动物双杂交系统表明，CBP和p300通过CREB结合域与mArnt3相互作用。GST下拉实验证实了mArnt3和CBP之间的体内相互作用。结论：综上所述，这些结果表明，mArnt3/mClock异源二聚体通过CBP或p300与异源二聚体中的mArnt3相互作用发挥其转激活活性，mClock在转激活过程中发挥结构性或调节性作用。
Background: The Arnt3 (also termed as BMAL1 or MOP3)/Clock heterodimer is a positive regulator of circadian rhythm and activates the transcription of target genes such as per1 and vasopressin.Results: We investigated the transcriptional mechanism of mArnt3/mClock heterodimer. While mClock did not possess any distinct activation domain, mArnt3 contained a transcriptional activation domain at the most C-terminal end, the activity of which was not expressed, even in the one hybrid system, until it was bound by mClock. It has been suggested that mClock plays a regulatory or structural role in exerting a transcription enhancing effect of the mArnt3/mClock heterodimer. Deletion proceeding from amino acids 559-492 of mClock markedly reduced the transactivation activity of mArnt3/mClock heterodimer, in consistence with the results of the Clock-Delta 19 mutant. Yeast and mammalian two-hybrid systems revealed that CBP and p300 interacted with mArnt3 via the CREB binding domain. The In vivo interaction between mArnt3 and CBP was confirmed by the GST pull down assay.Conclusions: Taken together, these results suggest that the mArnt3/mClock heterodimer exerted its transactivation activity via CBP or p300 interacting with mArnt3 in the heterodimer with mClock playing a structural or regulatory role in the transactivation process.