Histone Methylation Regulator PTIP Is Required for PPARγ and C/EBPα Expression and Adipogenesis

被引:121
作者
Cho, Young-Wook [1 ]
Hong, SunHwa [1 ]
Jin, Qihuang [1 ]
Wang, Lifeng [1 ]
Lee, Ji-Eun [1 ]
Gavrilova, Oksana [2 ]
Ge, Kai [1 ]
机构
[1] NIDDKD, Nucl Receptor Biol Sect, CEB, NIH, Bethesda, MD 20892 USA
[2] NIDDKD, Mouse Metab Core Lab, NIH, Bethesda, MD 20892 USA
关键词
TRANSCRIPTIONAL CONTROL; GENE; CHROMATIN; PROTEIN; COACTIVATOR; DOMAIN; BETA; FAT;
D O I
10.1016/j.cmet.2009.05.010
中图分类号
Q2 [细胞生物学];
学科分类号
071009 ; 090102 ;
摘要
PPAR gamma and C/EBP alpha cooperate to control preadipocyte differentiation (adipogenesis). However, the factors that regulate PPAR gamma and C/EBP alpha expression during adipogenesis remain largely unclear. Here, we show PTIP, a protein that associates with histone H3K4 methyltransferases, regulates PPAR gamma and C/EBP alpha expression in mouse embryonic fibroblasts (MEFs) and during preadipocyte differentiation. PTIP deletion in MEFs leads to marked decreases of PPAR gamma expression and PPAR gamma-stimulated C/EBP alpha expression. Further, PTIP is essential for induction of PPAR gamma and C/EBP alpha expression during preadipocyte differentiation. Deletion of PTIP impairs the enrichment of H3K4 trimethylation and RNA polymerase II on PPAR gamma and C/EBP alpha promoters. Accordingly, PTIP-/- MEFs and preadipocytes all show striking defects in adipogenesis. Rescue of the adipogenesis defect in PTIP-/- MEFs requires coexpression of PPAR gamma and C/EBP alpha. Finally, deletion of PTIP in brown adipose tissue significantly reduces tissue weight. Thus, by regulating PPAR gamma and C/EBP alpha expression, PTIP plays a critical role in adipogenesis.
引用
收藏
页码:27 / 39
页数:13
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