Reactome | PDK4 gene expression is stimulated by PPARG:RXRA:MLL4,(MLL3)-ASCOM complex

PDK4 gene expression is stimulated by PPARG:RXRA:MLL4,(MLL3)-ASCOM complex

Stable Identifier

R-HSA-9859119

Type

Reaction [omitted]

Species

Homo sapiens

Compartment

nucleoplasm, mitochondrial matrix

ReviewStatus

3/5

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Gene expression (Transcription) (Homo sapiens)

- Epigenetic regulation of gene expression (Homo sapiens)
  - Epigenetic regulation by WDR5-containing histone modifying complexes (Homo sapiens)
    - Epigenetic regulation of gene expression by MLL3 and MLL4 complexes (Homo sapiens)
      - Epigenetic regulation of adipogenesis genes by MLL3 and MLL4 complexes (Homo sapiens)
        
        MLL4 and MLL3 complexes regulate expression of PPARG target genes in adipogenesis and hepatic steatosis (Homo sapiens)
        
        PDK4 gene expression is stimulated by PPARG:RXRA:MLL4,(MLL3)-ASCOM complex (Homo sapiens)

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PDK4 gene expression is stimulated by PPARG:RXRA:MLL4,(MLL3)-ASCOM complex

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Expression of the PDK4 gene, encoding mitochondrial Pyruvate dehydrogenase acetyl-transferring kinase isozyme 4, also known as PDHK4, which regulates the TCA cycle, is positively regulated in fat tissue by the PPARG:RXRA heterodimer and KMT2C (MLL3)/KMT2D (MLL4) histone methyltransferase complexes. In primary human white adipocytes undergoing browning, the PDK4 expression is significantly increased upon treatment with the PPARG agonist rosiglitazone (Barquissau et al. 2016). In mouse 3T3-L1 cell line-derived adipocytes, Pdk4 mRNA level is increased upon treatment with the PAPRG agonist rosiglitazone (Allen et al. 2006). Expression of the Pdk4 gene is severely reduced in differentiating mouse brown preadipocytes expressing histone H3.3 K4M mutant or Kmt2c (Mll3) and Kmt2d (Mll4) with deleted SET domains (Jang et al. 2019: RNA-seq, supplementary information).

Literature References

PubMed ID	Title	Journal	Year
27110487	White-to-brite conversion in human adipocytes promotes metabolic reprogramming towards fatty acid anabolic and catabolic pathways Barquissau, V, Tavernier, G, Beuzelin, D, Guillou, H, Beranger, GE, Amri, EZ, Moro, C, Mairal, A, Roussel, B, Pisani, DF, Langin, D, Montagner, A, Marques, MA	Mol Metab	2016