Genome-wide analysis of JMJD1A and PPAR? binding in immortalized, differentiated preadipocytes derived from inguinal subcutaneous white adipose tissue.

In acute cold stress in mammals, JMJD1A, an H3K9 demethylase, up-regulates thermogenic gene expressions through ß-adrenergic signaling in brown adipose tissue (BAT). Aside BAT-driven thermogenesis, mammals also have another mechanism to cope with long-term cold stress by inducing the browning of subcutaneous white adipose tissue (scWAT). Here, we show that this occurs through a two-step process that requires both ß-adrenergic dependent phosphorylation of S265 and demethylation of H3K9me2 by JMJD1A. The histone demethylation independent acute Ucp1 induction in BAT and demethylation dependent chronic Ucp1 expression in beige-scWAT provide complementary molecular mechanisms to ensure an ordered transition between acute and chronic adaptation to cold stress. JMJD1A mediates two major signaling pathways, namlely ß-adrenergic receptor and PPAR? activation, via PRDM16-PPAR?-P-JMJD1A complex for beige adipogenesis. Overall design: Preadipocytes derived from inguinal subcutaneous white adipose tissue were immortalized. Preadipocytes were differentiated for ChIP-seq analysis of JMJD1A and PPAR? using Illumina HiSeq 2500.