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

来源：

CELL METABOLISM | 2009年 / 10卷 / 01期

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

页码：27 / 39

页数：13

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