A nuclear function of β-arrestin1 in GPCR signaling:: Regulation of histone acetylation and gene transcription
A nuclear function of β-arrestin1 in GPCR signaling:: Regulation of histone acetylation and gene transcription
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DOI：
10.1016/j.cell.2005.09.011
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发表时间：
2005-12-02
期刊：
影响因子：
64.5
通讯作者：
Ma, L
中科院分区：
文献类型：
--
作者：
Kang, JH;Shi, YF;Ma, L
染色质修饰被认为是调节基因表达以对环境变化产生协调反应的基本机制，然而，它是否可以由最大的表面受体家族G蛋白偶联受体（GPCR）介导的信号直接调节尚不清楚。在这里，我们表明，刺激δ-阿片受体，GPCR家族的成员，诱导β-arrestin 1（β arr 1），这是以前已知的细胞溶质调节和支架GPCR信号的核转位。响应于受体激活，β arr 1易位到细胞核，并选择性地富集在特定的启动子，如p27和c-fos的启动子，在那里它促进组蛋白乙酰转移酶p300的募集，从而增强局部组蛋白H4乙酰化和这些基因的转录。我们的研究结果揭示了一种新的功能β arr 1作为一个细胞质-核信使GPCR信号，并阐明了直接GPCR信号从细胞膜到细胞核通过信号依赖性组蛋白修饰的表观遗传机制。
Chromatin modification is considered to be a fundamental mechanism of regulating gene expression to generate coordinated responses to environmental changes, however, whether it could be directly regulated by signals mediated by G protein-coupled receptors (GPCRs), the largest surface receptor family, is not known. Here, we show that stimulation of delta-opioid receptor, a member of the GPCR family, induces nuclear translocation of beta-arrestin 1 (beta arr1), which was previously known as a cytosolic regulator and scaffold of GPCR signaling. In response to receptor activation, beta arr1 translocates to the nucleus and is selectively enriched at specific promoters such as that of p27 and c-fos, where it facilitates the recruitment of histone acetyltransferase p300, resulting in enhanced local histone H4 acetylation and transcription of these genes. Our results reveal a novel function of beta arr1 as a cytoplasm-nucleus messenger in GPCR signaling and elucidate an epigenetic mechanism for direct GPCR signaling from cell membrane to the nucleus through signal-dependent histone modification.