Genome-wide ChIP-seq profiling of PPARγ/RXR target sites and gene program during adipogenesis

Peroxisome proliferator-activated receptors (PPARs) are nuclear receptors which bind to DNA as heterodimers with members of the retinoid X receptor family. PPARγ is an important regulator of adipocyte differentiation and function. In addition to driving the adipogenic process, PPARγ activates directly a large number of genes involved in lipid metabolism.

Using ChIP combined with deep sequencing we have generated a genome-wide map of PPARγ-RXR binding to chromatin as well as the activation of associated target genes during differentiation of murine 3T3-L1 adipocytes. Our analysis shows that target sites/genes attain RXR and PPARγ occupancy at different time points and that sites are often co-occupied by C/EBP factors. Coupling this analysis with RNAPII occupancy throughout adipogenesis revealed that PPARg:RXR is specifically associated with induced genes involved in diverse processes including lipid and glucose metabolism.

These results provide an excellent basis for extensive analyses of the regulatory network controlled by PPARγ during adipocyte differentiation and in the mature adipocytes.

This work is supported by grants to the EU FP6 STREP project X-TRA-NET, EU FP6 IP HEROIC and grants from the Lundbeck Foundation and the Danish Natural Science Research Council.