Propagation of adipogenic signals through an epigenomic transition state.
The transcriptional mechanisms by which temporary exposure to developmental signals instigates adipocyte differentiation are unknown. During early adipogenesis, we find transient enrichment of the glucocorticoid receptor (GR), CCAAT/enhancer-binding protein beta (CEBPbeta), p300, mediator subunit 1, and histone H3 acetylation near genes involved in cell proliferation, development, and differentiation, including the gene encoding the master regulator of adipocyte differentiation, peroxisome proliferator-activated receptor gamma2 (PPARgamma2). Occupancy and enhancer function are triggered by adipogenic signals, and diminish upon their removal. GR, which is important for adipogenesis but need not be active in the mature adipocyte, functions transiently with other enhancer proteins to propagate a new program of gene expression that includes induction of PPARgamma2, thereby providing a memory of the earlier adipogenic signal. Thus, the conversion of preadipocyte to adipocyte involves the formation of an epigenomic transition state that is not observed in cells at the beginning or end of the differentiation process.
Steger
David J
DJ
Division of Endocrinology, Diabetes, and Metabolism, Department of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania 19104, USA.
Grant
Gregory R
GR
Schupp
Michael
M
Tomaru
Takuya
T
Lefterova
Martina I
MI
Schug
Jonathan
J
Manduchi
Elisabetta
E
Stoeckert
Christian J
CJ
Lazar
Mitchell A
MA
D000107:Acetylation; D050156:Adipogenesis / Q000502:physiology*; D000818:Animals; D022782:CCAAT-Enhancer-Binding Protein-beta / Q000378:metabolism; D002460:Cell Line; D044127:Epigenesis, Genetic; D006657:Histones / Q000378:metabolism; D051379:Mice; D047492:Peroxisome Proliferator-Activated Receptors / Q000378:metabolism; D011965:Receptors, Glucocorticoid / Q000378:metabolism; D015398:Signal Transduction
D022782:CCAAT-Enhancer-Binding Protein-beta; C545013:Cebpb protein, mouse; D006657:Histones; D047492:Peroxisome Proliferator-Activated Receptors; D011965:Receptors, Glucocorticoid