Promoter-specific recruitment of PPARG in adipocytes depends on GPS2-dependent stabilization of histone demethylase KDM4A/JMJD2 [KDM4A]

ABSTRACT: Timely and selective recruitment of transcription factors to their appropriate DNA-binding sites represents a critical step in regulating gene activation; however the regulatory strategies underlying each factor’s effective recruitment to specific promoter and/or enhancer regions are not fully understood. Here, we identify an unexpected regulatory mechanism by which promoter-specific binding, and therefore function, of PPARG in adipocytes requires G protein Suppressor 2 (GPS2) to prime the local chromatin environment via inhibition of the ubiquitin ligase RNF8 and stabilization of the H3K9 histone demethylase KDM4A/JMJD2. Integration of genome-wide profiling data indicates that the pioneering activity of GPS2/KDM4A is required for PPARG mediated regulation of a specific transcriptional program, including the lipolytic enzymes ATGL and HSL. Hence, our findings reveal that GPS2 exerts a biologically important function in adipose tissue lipid mobilization by directly regulating ubiquitin signaling and indirectly modulating chromatin remodeling to prime selected genes for activation.

ORGANISM(S): Mus musculus

PROVIDER: GSE57778 | GEO | 2014/07/14

SECONDARY ACCESSION(S): PRJNA248078

REPOSITORIES: GEO