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
5/5
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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, also known as Lipin) gene, encoding magnesium-dependent phosphatidate phosphatase enzyme responsible for conversion of phosphatidic acid (PA) to diacylglycerol (DAG) during triglyceride, phosphatidylcholine and phosphatidylethanolamine biosynthesis (reviewed in Welcome et al. 2025), is positively regulated by PPARG:RXRA heterodimers and KMT2C (MLL3)/KMT2D (MLL4) histone methyltransferase complexes. In differentiating primary human adipocytes, LPIN1 mRNA levels are reduced upon antisense-mediated knockdown of PPARG mRNA (Perera et al. 2006, Supplementary materials Table 2). Expression of LPIN1 splicing isoform beta (Lipin-beta) 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, but this correlation is not seen for LPIN1 splicing isoform alpha (Lipin-alpha) (Yao-Borengasser et al. 2008). This implies that alpha and beta 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

Perera, RJ, Marcusson, EG, Koo, S, Kang, X, Kim, Y, White, N, Dean, NM

Gene 2006
18697866 Stearoyl-coenzyme A desaturase 1 gene expression increases after pioglitazone treatment and is associated with peroxisomal proliferator-activated receptor-gamma responsiveness

Yao-Borengasser, A, Rassouli, N, Varma, V, Bodles, AM, Rasouli, N, Unal, R, Phanavanh, B, Ranganathan, G, McGehee, RE, Kern, PA

J Clin Endocrinol Metab 2008
Participants
Input
Output
Participates
as an event of
This event is regulated
Positively by
Regulator
Activated PPARG:RXRA:LPIN1 gene:H3K4me1-Nucleosomes:MLL4,(MLL3)-ASCOM [nucleoplasm] (Homo sapiens)
Active Unit
MLL4-ASCOM,(MLL3-ASCOM) [nucleoplasm]
PPARG natural ligands [nucleoplasm]
PPARG:RXRA [nucleoplasm]
RXRA natural ligands [nucleoplasm]
(NCOA1, NCOA2, NCOA3) [nucleoplasm]
Inferred From
Lpin1 gene expression is stimulated by Mll4,(Mll3) complex (Mus musculus)
Authored
Orlic-Milacic, M  (2024-01-18)
Reviewed
Aberin, MAE  (2025-10-31)
Wang, SP  (2025-10-31)
Created
Orlic-Milacic, M  (2024-01-18)
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