Chromatin accessibility and transcription factor binding at the PPARγ2 promoter during adipogenesis is protein kinase A-dependent.
The nuclear hormone receptor peroxisome proliferator-activated receptor gamma (PPARγ) is a ligand-activated transcription factor that specifies formation of the adipocyte lineage. PPARγ also serves as a primary target for the treatment of type 2 diabetes, illustrating both its medical relevance as well as the need to understand fundamental aspects of PPARγ expression and function. Here, we characterize molecular changes that occur at the PPARγ2 promoter within the first several hours of adipocyte differentiation in culture. Our results demonstrate that changes in chromatin accessibility at the PPARγ2 promoter and occupancy of the promoter by the c-Fos transcription factor occur within an hour of the onset of differentiation, followed closely by the binding of the CCAAT/enhancer binding protein beta (C/EBPβ) transcription factor. All three events show a remarkable dependency on protein kinase A (PKA) activity. These results reflect novel requirements for the PKA signaling pathway and reinforce the importance of PKA function during the onset of adipocyte differentiation.
Xiao
Hengyi
H
Department of Cell Biology, University of Massachusetts Medical School, Worcester, Massachusetts 01655, USA.
Leblanc
Scott E
SE
Wu
Qiong
Q
Konda
Silvana
S
Salma
Nunciada
N
Marfella
Concetta G A
CG
Ohkawa
Yasuyuki
Y
Imbalzano
Anthony N
AN
D050156:Adipogenesis / Q000502:physiology*; D000818:Animals; D002460:Cell Line; D002843:Chromatin / Q000502:physiology*; D017868:Cyclic AMP-Dependent Protein Kinases / Q000378:metabolism*; D005786:Gene Expression Regulation / Q000502:physiology; D006801:Humans; D051379:Mice; D047495:PPAR gamma / Q000235:genetics / Q000378:metabolism*; D011401:Promoter Regions, Genetic / Q000235:genetics*; D011485:Protein Binding / Q000502:physiology; D014157:Transcription Factors / Q000378:metabolism*
D002843:Chromatin; D047495:PPAR gamma; D014157:Transcription Factors; D017868:Cyclic AMP-Dependent Protein Kinases