PPARγ and C/EBPα cooperate to control preadipocyte differentiation (adipogenesis). However, the factors that regulate PPARγ and C/EBPα expression during adipogenesis remain largely unclear. Here, we show PTIP, a protein that associates with histone H3K4 methyltransferases, regulates PPARγ and C/EBPα expression in mouse embryonic fibroblasts (MEFs) and during preadipocyte differentiation. PTIP deletion in MEFs leads to marked decreases of PPARγ expression and PPARγ-stimulated C/EBPα expression. Further, PTIP is essential for induction of PPARγ and C/EBPα expression during preadipocyte differentiation. Deletion of PTIP impairs the enrichment of H3K4 trimethylation and RNA polymerase II on PPARγ and C/EBPα promoters. Accordingly, PTIP-/- MEFs and preadipocytes all show striking defects in adipogenesis. Rescue of the adipogenesis defect in PTIP-/- MEFs requires coexpression of PPARγ and C/EBPα. Finally, deletion of PTIP in brown adipose tissue significantly reduces tissue weight. Thus, by regulating PPARγ and C/EBPα expression, PTIP plays a critical role in adipogenesis.
|Original language||English (US)|
|Number of pages||13|
|State||Published - Jul 8 2009|
ASJC Scopus subject areas
- Molecular Biology
- Cell Biology