Extensive chromatin remodelling 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/EBP beta and -delta) to transcription factor 'hotspots'. Our results demonstrate that C/EBP beta marks a large number of these transcription factor 'hotspots' before induction of differentiation and chromatin remodelling and is required for their establishment. Furthermore, a subset of early remodelled 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. The EMBO Journal (2011) 30, 1459-1472. doi:10.1038/emboj.2011.65; Published online 22 March 2011 Subject Categories: chromatin & transcription