Genome-Wide Profiling of PPAR :RXR and RNA Polymerase II Occupancy
Downloaded from genesdev.cshlp.org on September 26, 2021 - Published by Cold Spring Harbor Laboratory Press Genome-wide profiling of PPAR␥:RXR and RNA polymerase II occupancy reveals temporal activation of distinct metabolic pathways and changes in RXR dimer composition during adipogenesis Ronni Nielsen,1,4 Thomas Åskov Pedersen,1,4 Dik Hagenbeek,2,4 Panagiotis Moulos,2,3 Rasmus Siersbæk,1 Eva Megens,2 Sergei Denissov,2 Michael Børgesen,1 Kees-Jan Francoijs,2 Susanne Mandrup,1,6 and Hendrik G. Stunnenberg2,5 1Department of Biochemistry and Molecular Biology, University of Southern Denmark, 5230 Odense M, Denmark; 2Department of Molecular Biology, Nijmegen Center for Molecular Life Sciences, Radboud University, 6500 HB Nijmegen, The Netherlands; 3Metabolic Engineering and Bioinformatics Group, Institute of Biological Research and Biotechnology, National Hellenic Research Foundation, 11635 Athens, Greece The nuclear receptor peroxisome proliferator-activated receptor ␥ (PPAR␥) is a key regulator of adipocyte differentiation in vivo and ex vivo and has been shown to control the expression of several adipocyte-specific genes. In this study, we used chromatin immunoprecipitation combined with deep sequencing to generate genome-wide maps of PPAR␥ and retinoid X receptor (RXR)-binding sites, and RNA polymerase II (RNAPII) occupancy at very high resolution throughout adipocyte differentiation of 3T3-L1 cells. We identify >5000 high-confidence shared PPAR␥:RXR-binding sites in adipocytes and show that during early stages of differentiation, many of these are preoccupied by non-PPAR␥ RXR-heterodimers. Different temporal and compositional patterns of occupancy are observed. In addition, we detect co-occupancy with members of the C/EBP family.
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