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Regulation of chromatin accessibility by GPS2‐mediated inhibition of ubiquitin signaling on selected promoters
Author(s) -
Cardamone Maria,
Tanasa Bogdan,
Huang Jiawen,
Cederquist Carly,
Rosenfeld Michael,
Perissi Valentina
Publication year - 2015
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.29.1_supplement.880.28
Subject(s) - biology , transcription factor , chromatin , microbiology and biotechnology , transcriptional regulation , chromatin immunoprecipitation , chromatin remodeling , demethylase , promoter , genetics , gene , histone , gene expression
G‐protein Suppressor 2 (GPS2) is a small protein, originally identified while screening for suppressors of Ras activation in the yeast pheromone response pathway, that exerts critical anti‐inflammatory roles in adipocytes and macrophages and is significantly downregulated in human obesity. While GPS2 is known to interact with various transcriptional regulators, including chromatin‐remodeling enzymes, DNA repair proteins and DNA‐binding transcription factors, a clear understanding of the molecular mechanism of GPS2 transcriptional function remains strikingly incomplete. To investigate the molecular mechanism of GPS2 genomic actions, we determined GPS2 genome‐wide binding profile in undifferentiated 3T3‐L1 pre‐adipocytes and differentiated adipocytes by ChIPseq. Our results suggest that GPS2 is specifically required to regulate a defined transcriptional program including genes important for lipid mobilization and fatty acid oxidation. Furthermore, integration of GPS2 localization profile with comparable ChIPseq datasets for the corepressors NCoR and SMRT, and for the nuclear receptors PPARg and RXR, has led to the identification of a novel regulatory strategy for PPARγamma‐mediated transcription based on the control of promoter architecture via stabilization of histone demethylase KDM4A and regulation of PolII pausing. These findings, together with our recent report of GPS2‐mediated inhibition of JNK activation in adipose tissue and macrophages, indicates that the ability of GPS2 to regulate ubiquitin signaling, both inside and outside the nucleus, plays a central role in key metabolic organs.