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

Young Wook Cho; Sun Hwa Hong; Qihuang Jin; Lifeng Wang; Ji Eun Lee; Oksana Gavrilova; Kai Ge

doi:10.1016/j.cmet.2009.05.010

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

Young Wook Cho, Sun Hwa Hong, Qihuang Jin, Lifeng Wang, Ji Eun Lee, Oksana Gavrilova, Kai Ge

Research output: Contribution to journal › Article › peer-review

109 Scopus citations

Abstract

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)
Pages (from-to)	27-39
Number of pages	13
Journal	Cell Metabolism
Volume	10
Issue number	1
DOIs	https://doi.org/10.1016/j.cmet.2009.05.010
State	Published - Jul 8 2009

Keywords

HUMDISEASE

ASJC Scopus subject areas

Physiology
Molecular Biology
Cell Biology

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10.1016/j.cmet.2009.05.010

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title = "Histone Methylation Regulator PTIP Is Required for PPARγ and C/EBPα Expression and Adipogenesis",

abstract = "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.",

keywords = "HUMDISEASE",

author = "Cho, {Young Wook} and Hong, {Sun Hwa} and Qihuang Jin and Lifeng Wang and Lee, {Ji Eun} and Oksana Gavrilova and Kai Ge",

note = "Funding Information: We thank G. Dressler for PTIP conditional KO mice; B. Kahn for aP2-Cre mice line 1; G. Darlington for C/EBP α +/− and C/EBP α −/− cell lines; D. Lane for 3T3-L1 cell line; H. Yu, G. Poy, W. Jou, and T. Chanturiya for technical assistance; and A. McPherron for critical reading of the manuscript. This work was supported by the Intramural Research Program of the NIDDK, NIH to K.G. ",

year = "2009",

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doi = "10.1016/j.cmet.2009.05.010",

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T1 - Histone Methylation Regulator PTIP Is Required for PPARγ and C/EBPα Expression and Adipogenesis

AU - Cho, Young Wook

AU - Hong, Sun Hwa

AU - Jin, Qihuang

AU - Wang, Lifeng

AU - Lee, Ji Eun

AU - Gavrilova, Oksana

AU - Ge, Kai

N1 - Funding Information: We thank G. Dressler for PTIP conditional KO mice; B. Kahn for aP2-Cre mice line 1; G. Darlington for C/EBP α +/− and C/EBP α −/− cell lines; D. Lane for 3T3-L1 cell line; H. Yu, G. Poy, W. Jou, and T. Chanturiya for technical assistance; and A. McPherron for critical reading of the manuscript. This work was supported by the Intramural Research Program of the NIDDK, NIH to K.G.

PY - 2009/7/8

Y1 - 2009/7/8

N2 - 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.

AB - 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.

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ER -

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

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