A nuclear function of beta-arrestin1 in GPCR signaling: regulation of histone acetylation and gene transcription

Jiuhong Kang; Yufeng Shi; Bin Xiang; Bin Qu; Wenjuan Su; Min Zhu; Min Zhang; Guobin Bao; Feifei Wang; Xiaoqing Zhang; Rongxi Yang; Fengjuan Fan; Xiaoqing Chen; Gang Pei; Lan Ma

doi:10.1016/j.cell.2005.09.011

A nuclear function of beta-arrestin1 in GPCR signaling: regulation of histone acetylation and gene transcription

Cell. 2005 Dec 2;123(5):833-47. doi: 10.1016/j.cell.2005.09.011.

Authors

Jiuhong Kang¹, Yufeng Shi, Bin Xiang, Bin Qu, Wenjuan Su, Min Zhu, Min Zhang, Guobin Bao, Feifei Wang, Xiaoqing Zhang, Rongxi Yang, Fengjuan Fan, Xiaoqing Chen, Gang Pei, Lan Ma

Affiliation

¹ 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.

PMID: 16325578
DOI: 10.1016/j.cell.2005.09.011

Abstract

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.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Acetylation
Active Transport, Cell Nucleus / physiology
Animals
Arrestins / genetics
Arrestins / metabolism*
Cell Line
Cell Nucleus / metabolism*
Chromatin / metabolism
Cyclin-Dependent Kinase Inhibitor p27 / genetics
Cyclin-Dependent Kinase Inhibitor p27 / metabolism
Epigenesis, Genetic
Gene Expression Regulation*
Histones / metabolism*
Humans
Mice
Mice, Knockout
Promoter Regions, Genetic
Proto-Oncogene Proteins c-fos / genetics
Proto-Oncogene Proteins c-fos / metabolism
Receptors, G-Protein-Coupled / genetics
Receptors, G-Protein-Coupled / metabolism*
Receptors, Opioid, delta / genetics
Receptors, Opioid, delta / metabolism*
Recombinant Fusion Proteins / genetics
Recombinant Fusion Proteins / metabolism
Signal Transduction / physiology
Transcription, Genetic*
beta-Arrestin 1
beta-Arrestins
p300-CBP Transcription Factors / metabolism

Substances

ARRB1 protein, human
Arrb1 protein, mouse
Arrestins
Chromatin
Histones
Proto-Oncogene Proteins c-fos
Receptors, G-Protein-Coupled
Receptors, Opioid, delta
Recombinant Fusion Proteins
beta-Arrestin 1
beta-Arrestins
Cyclin-Dependent Kinase Inhibitor p27
p300-CBP Transcription Factors