Expression of PPARG

Stable Identifier
R-HSA-381283
Type
Reaction [omitted]
Species
Homo sapiens
Compartment
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The transcription factors CEBPB, CEBPD, and KLF5 simultaneously bind the PPARG promoter and synergistically activate transcription of the PPARG gene. These three factors activate transcription after initial stimulation of adipocyte differentiation but then are replaced by CEBPA within 10 days. CEBPA and other factors may be responsible for long term maintenance of PPARG expression and the differentiated state.
Pre-adipose tissue contains both the widely expressed PPARG isoform 1 mRNA and the more tissue-specific PPARG isoform 2. The PPARG isoform 2 mRNA is translated to yield PPARG isoform 2 protein, which has 505 amino acid residues (57 KDa) and is the longest of the 4 observed variants. Isoform 2 is specific to preadipose and adipose tissue (Mukherjee et al. 1997). Confusingly, the longest variant is called isoform 1 in some publications.
In mouse, by 10 days after induction of adipocyte differentiation Cebpa, but neither Cebpb nor Cebpd, is detectable at the Pparg promoter. While adipocyte differentiation can proceed without Cebpa, adipocytes differentiated from Cebpa-knockout cells are insulin insensitive due to a defect in Glut4 (Slc2a4) vesicle trafficking.
The adipogenesis regulatory factor (ADIRF, aka AFRO, APM2, C10orf116) promotes adipogenic differentiation and stimulates transcription initiation of master adipogenesis factors like PPARG and CEBPA (Ni et al. 2013).

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This event is regulated
Negatively by
Regulator
Summation

As inferred from mouse, NF-kappaB inhibits expression of PPARG in pre-adipocytes (Chae and Kwak 2003). TNFalpha represses PPARG via NF-kappaB (Chae and Kwak 2003, Kurebayashi et al. 2001, Xing et al. 1997).

Regulator
Summation

As inferred from mouse 3T3-L1 cells, Wnt-1 and Wnt-10b inhibit PPARG expression (Ross et al. 2000, Bennett et al. 2002) by activating COUP-TFII (NR2F2) which recruits the SMRT repressor complex to the PPARG gene (Okamura et al. 2009).

Regulator
Summation

As inferred from mouse, TGF-beta inhibits expression of PPARG.

Positively by
Regulator
Summation

As inferred from mouse homologs, ZNF467 (ZFP467) binds the promoter of the PPARG gene and recruits a histone deacetylase complex to activate transcription of PPARG.

Regulator
Summation

Activation of PPARG transcription by CEPBA is inferred from mouse.

Regulator
Summation

ZNF638 cooperates together with CEBPB and CEBPD at the promoter of the PPARG gene to activate transcription (inferred from mouse homologs).

Regulator
Summation

As inferred from mouse, SREBP1A and SREBP2 bind to the PPARG1 and PPARG2 promoters and activate transcription.

Inferred From
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