MED1 is a lipogenesis co-activator required for postnatal adipose expansion

MED1 often serves as a surrogate of the general transcription coactivator complex Mediator for identifying active enhancers. MED1 is required for phenotypic conversion of fibroblasts to adipocytes in vitro but its role in adipose development and expansion in vivo has not been reported. Here we show that MED1 is not generally required for transcription during adipogenesis in culture and that MED1 is dispensable for adipose development in mice. Instead, MED1 is required for postnatal adipose expansion and the induction of fatty acid and triglyceride synthesis genes after pups switch diet from high-fat maternal milk to carbohydrate-based chow. During adipogenesis, MED1 is dispensable for induction of lineage-determining transcription factors (TFs) PPAR? and C/EBPa but is required for lipid accumulation in the late phase of differentiation. Mechanistically, MED1 controls the induction of lipogenesis genes by facilitating lipogenic TF ChREBP- and SREBP1a-dependent recruitment of Mediator to active enhancers. Together, our ?ndings identify a cell- and gene-specific regulatory role of MED1 as a lipogenesis coactivator required for postnatal adipose expansion. Overall design: Expression profiling by RNA-Seq and nascent RNA-Seq at D7 of adipogenesis in brown or white preadipocytes in culture, RNA-Seq and adipoq+ adipocyte specific TRAP RNA-Seq in interscapular brown adipose tissue and inguinal white adipose tissue and ChIP-Seq profiling of histone H3K27ac, S5P-Pol II, S2P-Pol II, T7 and MED12 by ChIP-Seq and profiling of chromatin accessibility by ATAC-Seq, at D7 of adipogenesis of brown preadipocytes in culture.