Reactome | LPIN1 gene expression is stimulated by PPARG:RXRA:MLL4,(MLL3)-ASCOM complex

LPIN1 gene expression is stimulated by PPARG:RXRA:MLL4,(MLL3)-ASCOM complex

Stable Identifier

R-HSA-9859334

Type

Reaction [omitted]

Species

Homo sapiens

Compartment

nucleoplasm, endoplasmic reticulum membrane

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)
        
        LPIN1 gene expression is stimulated by PPARG:RXRA:MLL4,(MLL3)-ASCOM complex (Homo sapiens)

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LPIN1 gene expression is stimulated by PPARG:RXRA:MLL4,(MLL3)-ASCOM complex

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Expression of the LPIN1 (LPN) gene, encoding magnesium-dependent phosphatidate phosphatase enzyme responsible for conversion of phosphatidic acid (PA) to diacylglycerol (DAG) during triglyceride, phosphatidylcholine and phosphatidylethanolamine biosynthesis, is positively regulated by PPARG:RXRA heterodimers and KMT2C (MLL3)/KMT2D (MLL4) histone methyltransferase complexes. In differentiating primary human adipocytes, LPIN1 mRNA levels are significantly reduced upon antisense-mediated knockdown of PPARG mRNA (Perera et al. 2006, Supplementary materials Table 2). Expression of LPIN1 mRNA is increased in fat tissue of human subjects treated with PPARG agonist pioglitazone, and correlates with increased mRNA levels of other PPARG-responsive genes, such as SCD (Yao-Borengasser et al. 2008). Different splicing isoforms of LPIN1 may be differentially regulated by PPARG (Yao-Borengasser et al. 2008). Expression of the Lpin1 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
16380219	Identification of novel PPARgamma target genes in primary human adipocytes Dean, NM, Koo, S, Kim, Y, Marcusson, EG, Kang, X, Perera, RJ, White, N	Gene	2006
18697866	Stearoyl-coenzyme A desaturase 1 gene expression increases after pioglitazone treatment and is associated with peroxisomal proliferator-activated receptor-gamma responsiveness Kern, PA, Bodles, AM, Varma, V, Phanavanh, B, Rasouli, N, Unal, R, Rassouli, N, Ranganathan, G, Yao-Borengasser, A, McGehee, RE	J Clin Endocrinol Metab	2008