Expression of the PLIN2 gene, encoding Perilipin-2, also known as Adipophilin or ADFP or Adipose differentiation-related protein (ADRP), which localizes to lipid droplets, is positively regulated in fat tissue by the PPARG:RXRA heterodimer and KMT2C (MLL3)/KMT2D (MLL4) histone methyltransferase complexes. Treatment of mouse white preadipocyte cell line 3T3-L1 with PPARG agonists results in increased Plin2 mRNA levels (Bhalla et al. 2011). Ligand-activated PPARG:RXRA heterodimer (i.e. PPARG ligand, troglitazone or RXR ligand LG268) was shown to stimulate PLIN2 gene transcription in human trophoblasts (Bildirici et al. 2003). Expression of the PLIN2 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).

Based on a mouse model of hepatic steatosis, expression of the Plin2 gene is directly stimulated by Pparg2 and the MLL4 complex but negatively regulated by imatinib, an Abl1 kinase inhibitor that disrupts Abl1-mediated association between Pparg2 and the Mll4 complex (Kim et al. 2016).