GSE27826
Extensive Chromatin Remodeling and Establishment of Transcription Factor ''Hotspots'' during Early Adipogenesis
Adipogenesis is tightly controlled by a complex network of transcription factors  acting at different stages of differentiation. Peroxisome proliferator-activated receptor gamma (PPAR gamma) and CCAAT/enhancer binding protein (C/EBP) family members are key  regulators of this process. We have employed DNase I hypersensitive site analysis to  investigate the genome-wide changes in chromatin structure that accompany the binding  of adipogenic transcription factors. These analyses revealed a dramatic and dynamic  modulation of the chromatin landscape during the first hours of adipocyte differentiation  that coincides with cooperative binding of multiple early transcription factors (including  glucocorticoid receptor, retinoid X receptor, Stat5a, C/EBPbeta and -delta) to transcription  factor ''hotspots''. Our results demonstrate that C/EBPbeta marks a large number of these  transcription factor ''hotspots'' prior to induction of differentiation and chromatin  remodeling and is required for their establishment. Furthermore, a subset of early  remodeled C/EBP binding sites persists throughout differentiation and is later occupied  by PPAR gamma , indicating that early C/EBP family members, in addition to their well  established role in activation of PPAR gamma  transcription, may act as pioneering factors for  PPAR gamma  binding. Overall design: DNase I hypersensitive chromatin regions and transcription factor binding sites were identified at various time points of 3T3-L1 differentiation using DHS-seq and ChIP-seq, respectively.