Expression of CEBPA gene, encoding CCAAT/enhancer-binding protein alpha which functions as one of the master transcriptional regulators of adipocyte differentiation, is positively regulated in fat tissue by PPARG:RXRA heterodimer and KMT2C (MLL3)/KMT2D (MLL4) histone methyltransferases. In differentiating primary human adipocytes, CEBPA mRNA levels are significantly reduced upon antisense-mediated knockdown of PPARG mRNA (Perera et al. 2006, Supplementary materials Table 2). Based on a study in mouse embryonic fibroblasts (MEFs) in which Pparg was ectopically expressed, PPARG positively regulates CEBPA transcription in a ligand-dependent manner (Ge et a. 2008).

MEFs deficient for Paxip1 (Ptip), an accessory subunit of Mll3 and Mll4 complexes, show a severe defect in Pparg- and ligand-stimulated expression of endogenous Cebpa (Cho et al. 2009). In differentiating mouse brown preadipocytes, Paxip1 promotes recruitment of RNA Pol II to Cebpa gene promoter (Cho et al. 2009).

In mouse brown preadipocytes expressing histone 3 mutant H3.3 K4M, the expression of the Cebpa gene is severely reduced (Jang et al. 2019). Deletion of SET domains of Kmt2c (Mll3) and Kmt2d (Mll4) in mouse brown preadipocytes prevents induction of Cebpa during adipogenesis (Jang et al. 2019).