A Nuclear Function of β-Arrestin1 in GPCR Signaling: Regulation of Histone Acetylation and Gene Transcription

Laboratory of Molecular Cell Biology, Institute of Biochemistry and Cell Biology, Shanghai Institutes for Biological Sciences, The Graduate School, Chinese Academy of Sciences, Shanghai 200031, China.
Cell (Impact Factor: 32.24). 02/2006; 123(5):833-47. DOI: 10.1016/j.cell.2005.09.011
Source: PubMed


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 (betaarr1), which was previously known as a cytosolic regulator and scaffold of GPCR signaling. In response to receptor activation, betaarr1 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 betaarr1 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.

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    • "Recently, although b-arrestin2 was reported to participate in the initiation and progression of myeloid leukaemia (Fereshteh et al, 2012), the critical role of b-arrestin1 in human haematological malignancies remains unresolved. More interestingly, b-arrestin1 has the ability of nuclear translocation and histone H4 acetylation modification with the delta-opioid receptors activated (Kang et al, 2005). The acetylation status of histone H4 terminal tails is one component of chromatin remodelling and chromatin-based processes including gene expression (Brower-Toland et al, 2005). "
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