Epigenetic regulation of the NR4A orphan nuclear receptor NOR1 by histone acetylation.
Epigenetic regulation of the NR4A orphan nuclear receptor NOR1 by histone acetylation.
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组蛋白乙酰化对 NR4A 孤儿核受体 NOR1 的表观遗传调控。
DOI：
10.1016/j.febslet.2014.11.017
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发表时间：
2014
期刊：
影响因子：
3.5
通讯作者：
Bruemmer,Dennis
中科院分区：
文献类型：
--
作者：
Zhao,Yue;Nomiyama,Takashi;Findeisen,HannesM;Qing,Hua;Aono,Jun;Jones,KarrieL;Heywood,ElizabethB;Bruemmer,Dennis
核受体NOR1是一种即刻-早期反应基因，与转录调控细胞增殖有关。由于NOR1的表达水平是通过cAMP反应元件结合(CREB)蛋白依赖的启动子激活而快速诱导的，我们研究了组蛋白乙酰化在这种瞬时诱导中的作用。我们证明，NOR1的转录是由组蛋白去乙酰酶(HDAC)抑制和HDAC1和HDAC3耗尽诱导的。HDAC抑制激活了NOR1启动子，增加了组蛋白乙酰化，并增加了磷酸化CREB对该启动子的募集。此外，HDAC抑制增加了CREB的Ser133磷酸化，增强了Nor1蛋白的稳定性。这些数据概述了以前未知的NOR1调节机制，并阐明了组蛋白乙酰化在NOR1快速诱导中的关键作用。
The nuclear receptorNOR1is an immediate‐early response gene implicated in the transcriptional control of proliferation. Since the expression level ofNOR1is rapidly induced through cAMP response element binding (CREB) protein‐dependent promoter activation, we investigated the contribution of histone acetylation to this transient induction. We demonstrate thatNOR1transcription is induced by histone deacetylase (HDAC) inhibition and by depletion of HDAC1 and HDAC3. HDAC inhibition activated theNOR1promoter, increased histone acetylation and augmented the recruitment of phosphorylated CREB to the promoter. Furthermore, HDAC inhibition increased Ser133 phosphorylation of CREB and augmented NOR1 protein stability. These data outline previously unrecognized mechanisms ofNOR1regulation and illustrate a key role for histone acetylation in the rapid induction ofNOR1.