| First Author | Cardamone MD | Year | 2014 |
| Journal | Cell Rep | Volume | 8 |
| Issue | 1 | Pages | 163-76 |
| PubMed ID | 24953653 | Mgi Jnum | J:259113 |
| Mgi Id | MGI:6148392 | Doi | 10.1016/j.celrep.2014.05.041 |
| Citation | Cardamone MD, et al. (2014) GPS2/KDM4A pioneering activity regulates promoter-specific recruitment of PPARgamma. Cell Rep 8(1):163-76 |
| abstractText | 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 peroxisome proliferator-activator receptor gamma (PPARgamma) 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 PPARgamma-mediated regulation of a specific transcriptional program, including the lipolytic enzymes adipose triglyceride lipase (ATGL) and hormone-sensitive lipase (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. |
