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
ReviewStatus
5/5
Locations in the PathwayBrowser
General
SVG |   | PPTX  | SBGN
Click the image above or here to open this reaction in the Pathway Browser
The layout of this reaction may differ from that in the pathway view due to the constraints in pathway layout
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
Participates
This event is regulated
Inferred From
Authored
Reviewed
Created
Cite Us!