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PPARA gene expression is stimulated by EBF2 and PPARG and repressed by ZNF423 and NuRD
Stable Identifier
R-HSA-9844536
Type
Reaction [omitted]
Species
Homo sapiens
Compartment
nucleoplasm
ReviewStatus
5/5
Locations in the PathwayBrowser
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Developmental Biology (Homo sapiens)
Adipogenesis (Homo sapiens)
Transcriptional regulation of brown and beige adipocyte differentiation (Homo sapiens)
Transcriptional regulation of brown and beige adipocyte differentiation by EBF2 (Homo sapiens)
PPARA gene expression is stimulated by EBF2 and PPARG and repressed by ZNF423 and NuRD (Homo sapiens)
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PPARA gene encodes peroxisome proliferator-activated receptor alpha, a ligand-activated transcription factor that functions as a key regulator of lipid metabolism in the brown adipose tissue. Based on mouse studies, expression of PPARA is directly regulated by the transcription factor EBF2, which binds to EBF binding elements in the PPARA gene (mouse studies Rajakumari et al. 2013; Shao et al. 2021). EBF2 facilitates recruitment of the PPARG:RXRA transcription factor complex to the PPAREs (peroxisome proliferator activator response elements) in the vicinity of EBF binding sites at the PPARA gene locus. PPARG augments PPARA gene transcription synergistically with EBF2 (mouse studies Rajakumari et al. 2013; Shao et al. 2021). EBF2-mediated recruitment of the BAF complex to regulatory sequences in the PPARA gene locus may precede EBF2-facilitated binding of PPARG to the PPARA gene locus (mouse study Shao et al. 2021). During differentiation of beige adipocytes in mouse inguinal white adipose tissue Ebf2 and Pparg synergistically upregulate Ppara mRNA levels (Stine et al. 2016). In mouse, depletion of DPF3, a subunit of the BAF chromatin remodeling complex that binds EBF2 and promotes transcription of EBF2 target genes, leads to downregulation of PPARA mRNA (Shapira et al. 2017). Blnc1 lncRNA, a cofactor of EBF2, significantly increases binding of EBF2 to the PPARA gene locus and EBF2-mediated transcriptional activation of PPARA (mouse study Zhao et al. 2014; mouse and human study Mi et al. 2017). PPARA gene expression is negatively regulated by ZNF423-mediated inhibition of EBF2 transcriptional activity, which is associated with the recruitment of the NuRD complex to the PPARA gene regulatory sequences (mouse study Shao et al. 2021).
Participants
Input
PPARA gene [nucleoplasm]
(Homo sapiens)
Output
PPARA [nucleoplasm]
(Homo sapiens)
Participates
as an event of
Transcriptional regulation of brown and beige adipocyte differentiation by EBF2 (Homo sapiens)
This event is regulated
Negatively by
Regulator
NuRD:ZNF423:EBF2, EBF2:Blnc1 lncRNA:HNRNPU:PPARA gene [nucleoplasm]
(Homo sapiens)
Active Unit
ZNF423 [nucleoplasm]
NuRD complex [nucleoplasm]
Positively by
Regulator
EBF2, EBF2:Blnc1 lncRNA:HNRNPU, Activated PPARG:RXRA:PPARA gene [nucleoplasm]
(Homo sapiens)
Active Unit
Activated PPARG:RXRA [nucleoplasm]
EBF2,EBF2:Blnc1 lncRNA:HNRNPU [nucleoplasm]
Inferred From
Ppara gene expression is stimulated by Ebf2 and Pparg and repressed by Znf423 and NuRD (Mus musculus)
Authored
Orlic-Milacic, M (2023-09-25)
Reviewed
Chun, TH (2023-11-29)
Created
Orlic-Milacic, M (2023-09-19)
© 2025
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