Extensive chromatin remodelling and establishment of transcription factor 'hotspots' during early adipogenesis

Rasmus Siersbæk, Ronni Nielsen, Sam John, Myong-Hee Sung, Songjoon Baek, Anne Loft, Gordon L Hager, Susanne Mandrup

Publikation: Bidrag til tidsskriftTidsskriftartikelForskningpeer review


Adipogenesis is tightly controlled by a complex network of transcription factors acting at different stages of differentiation. Peroxisome proliferator-activated receptor γ (PPARγ) 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/EBPβ and -δ) to transcription factor 'hotspots'. Our results demonstrate that C/EBPβ 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 PPARγ, indicating that early C/EBP family members, in addition to their well-established role in activation of PPARγ transcription, may act as pioneering factors for PPARγ binding.
TidsskriftThe EMBO Journal
Udgave nummer8
Sider (fra-til)1459-72
Antal sider14
StatusUdgivet - 20. apr. 2011


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