Antidiabetic Rosiglitazone Remodels the Adipocyte Transcriptome by Redistributing Transcription to PPARg-Driven Enhancers [Affymetrix]

ABSTRACT: Rosiglitazone (rosi) is a powerful insulin sensitizer, but serious toxicities have curtailed its widespread clinical use. Rosi functions as a high-affinity ligand for PPARg, the adipocyte-predominant nuclear receptor (NR). The classic model, involving binding of ligand to the NR on DNA, explains positive regulation of gene expression, but ligand-dependent repression is not well understood. We have now addressed this issue by studying the direct effects of rosiglitazone on gene transcription, using global run-on sequencing (GRO-seq). Rosi-induced changes in gene body transcription were pronounced after 10 minutes and correlated with steady-state mRNA levels as well as with transcription at nearby enhancers (eRNAs). Upregulated eRNAs occurred almost exclusively at PPARg binding sites, to whi

ORGANISM(S): Mus musculus

SUBMITTER: Hee-Woong Lim 

PROVIDER: E-GEOD-56688 | biostudies-arrayexpress |

REPOSITORIES: biostudies-arrayexpress