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

被引：120
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
收藏
页码：27 / 39
页数：13
相关论文
共 33 条
[1]   Adipose-selective targeting of the GLUT4 gene impairs insulin action in muscle and liver [J].
Abel, ED ;
Peroni, O ;
Kim, JK ;
Kim, YB ;
Boss, O ;
Hadro, E ;
Minnemann, T ;
Shulman, GI ;
Kahn, BB .
NATURE, 2001, 409 (6821) :729-733
[2]   A bivalent chromatin structure marks key developmental genes in embryonic stem cells [J].
Bernstein, BE ;
Mikkelsen, TS ;
Xie, XH ;
Kamal, M ;
Huebert, DJ ;
Cuff, J ;
Fry, B ;
Meissner, A ;
Wernig, M ;
Plath, K ;
Jaenisch, R ;
Wagschal, A ;
Feil, R ;
Schreiber, SL ;
Lander, ES .
CELL, 2006, 125 (02) :315-326
[3]   PTIP associates with MLL3-and MLL4-containing histone H3 lysine 4 methyltransferase complex [J].
Cho, Young-Wook ;
Hong, Teresa ;
Hong, SunHwa ;
Guo, Hong ;
Yu, Hong ;
Kim, Doyeob ;
Guszczynski, Tad ;
Dressler, Gregory R. ;
Copeland, Terry D. ;
Kalkum, Markus ;
Ge, Kai .
JOURNAL OF BIOLOGICAL CHEMISTRY, 2007, 282 (28) :20395-20406
[4]   Transcriptional control of adipocyte formation [J].
Farmer, Stephen R. .
CELL METABOLISM, 2006, 4 (04) :263-273
[5]   Transcription coactivator TRAP220 is required for PPARγ2-stimulated adipogenesis [J].
Ge, K ;
Guermah, M ;
Yuan, CX ;
Ito, M ;
Wallberg, AE ;
Spiegelman, BM ;
Roeder, RG .
NATURE, 2002, 417 (6888) :563-567
[6]   Mechanism for elimination of a tumor suppressor: Aberrant splicing of a brain-specific exon causes loss of function of Bin1 in melanoma [J].
Ge, K ;
DuHadaway, J ;
Du, W ;
Herlyn, M ;
Rodeck, U ;
Prendergast, GC .
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 1999, 96 (17) :9689-9694
[7]   Alternative mechanisms by which mediator subunit MED1/TRAP220 regulates peroxisome proliferator-activated receptor γ-stimulated adipogenesis and target gene expression [J].
Ge, Kai ;
Cho, Young-Wook ;
Guo, Hong ;
Hong, Teresa B. ;
Guermah, Mohamed ;
Ito, Mitsuhiro ;
Yu, Hong ;
Kalkum, Markus ;
Roeder, Robert G. .
MOLECULAR AND CELLULAR BIOLOGY, 2008, 28 (03) :1081-1091
[8]   A role for C/EBPβ in regulating peroxisome proliferator-activated receptor γ activity during adipogenesis in 3T3-L1 preadipocytes [J].
Hamm, JK ;
Park, BH ;
Farmer, SR .
JOURNAL OF BIOLOGICAL CHEMISTRY, 2001, 276 (21) :18464-18471
[9]   Adipose-specific peroxisome proliferator-activated receptor γ knockout causes insulin resistance in fat and liver but not in muscle [J].
He, WM ;
Barak, Y ;
Hevener, A ;
Olson, P ;
Liao, D ;
Le, J ;
Nelson, M ;
Ong, E ;
Olefsky, JM ;
Evans, RM .
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 2003, 100 (26) :15712-15717
[10]   Identification of JmjC domain-containing UTX and JMJD3 as histone H3 lysine 27 demethylases [J].
Hong, SunHwa ;
Cho, Young-Wook ;
Yu, Li-Rong ;
Yu, Hong ;
Veenstra, Timothy D. ;
Ge, Kai .
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 2007, 104 (47) :18439-18444
1234