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Extensive chromatin remodelling and establishment of transcription factor ‘hotspots’ during early adipogenesis
Author(s) -
Siersbæk Rasmus,
Nielsen Ronni,
John Sam,
Sung MyongHee,
Baek Songjoon,
Loft Anne,
Hager Gordon L,
Mandrup Susanne
Publication year - 2011
Publication title -
the embo journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 7.484
H-Index - 392
eISSN - 1460-2075
pISSN - 0261-4189
DOI - 10.1038/emboj.2011.65
Subject(s) - biology , transcription factor , adipogenesis , chromatin , ccaat enhancer binding proteins , pioneer factor , enhancer , transcription coregulator , microbiology and biotechnology , peroxisome proliferator activated receptor , genetics , dna binding protein , receptor , gene , mesenchymal stem cell
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.