Histone methylation regulator PTIP is required for PPARgamma and C/EBPalpha expression and adipogenesis.
PPARgamma and C/EBPalpha cooperate to control preadipocyte differentiation (adipogenesis). However, the factors that regulate PPARgamma and C/EBPalpha expression during adipogenesis remain largely unclear. Here, we show PTIP, a protein that associates with histone H3K4 methyltransferases, regulates PPARgamma and C/EBPalpha expression in mouse embryonic fibroblasts (MEFs) and during preadipocyte differentiation. PTIP deletion in MEFs leads to marked decreases of PPARgamma expression and PPARgamma-stimulated C/EBPalpha expression. Further, PTIP is essential for induction of PPARgamma and C/EBPalpha expression during preadipocyte differentiation. Deletion of PTIP impairs the enrichment of H3K4 trimethylation and RNA polymerase II on PPARgamma and C/EBPalpha promoters. Accordingly, PTIP(-/-) MEFs and preadipocytes all show striking defects in adipogenesis. Rescue of the adipogenesis defect in PTIP(-/-) MEFs requires coexpression of PPARgamma and C/EBPalpha. Finally, deletion of PTIP in brown adipose tissue significantly reduces tissue weight. Thus, by regulating PPARgamma and C/EBPalpha expression, PTIP plays a critical role in adipogenesis.
Cho
Young-Wook
YW
Nuclear Receptor Biology Section, CEB, National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health, Bethesda, MD 20892, USA.
Hong
SunHwa
S
Jin
Qihuang
Q
Wang
Lifeng
L
Lee
Ji-Eun
JE
Gavrilova
Oksana
O
Ge
Kai
K
D041721:3T3-L1 Cells; D052437:Adipocytes, Brown / Q000378:metabolism; D050156:Adipogenesis; D000818:Animals; D022763:CCAAT-Enhancer-Binding Protein-alpha / Q000378:metabolism*; D002352:Carrier Proteins / Q000235:genetics / Q000378:metabolism*; D002460:Cell Line; D004268:DNA-Binding Proteins; D005347:Fibroblasts / Q000378:metabolism; D000076983:Histone Methyltransferases; D011495:Histone-Lysine N-Methyltransferase / Q000378:metabolism*; D008745:Methylation; D051379:Mice; D018345:Mice, Knockout; D008822:Mice, Transgenic; D009687:Nuclear Proteins / Q000235:genetics / Q000378:metabolism*; D047495:PPAR gamma / Q000378:metabolism*
D022763:CCAAT-Enhancer-Binding Protein-alpha; D002352:Carrier Proteins; D004268:DNA-Binding Proteins; D009687:Nuclear Proteins; D047495:PPAR gamma; C412792:Paxip1 protein, mouse; D000076983:Histone Methyltransferases; D011495:Histone-Lysine N-Methyltransferase