The Multifaceted Roles of PRDM16: Adipose Biology and Beyond

The PRDM [PRDI-BFI (positive regulatory domain I-binding factor 1) and RIZ1 (retinoblastoma protein-interacting zinc finger gene 1) homologous domain containing] protein family is involved in a spectrum of biological processes including cell fate determination and development. These proteins regulate transcription through intrinsic chromatin-modifying activity or by complexing with histone-modifying or other nuclear proteins. Studies have indicated crucial roles for PRDM16 in the determination and function of brown and beige fat as well as in hematopoiesis and cardiac development, highlighting the importance of PRDM16 in developmental processes in different tissues. More recently, PRDM16 mutations were also identified in humans. The substantial progress in understanding the mechanism underlying the action of PRDM16 in adipose biology may have relevance to other PRDM family members, and this new knowledge has the potential to be exploited for therapeutic benefit.

TrendsPRDM16 plays a key role in adipose biology, regulating the determination and function of brown and beige fat. PRDM16 represents a promising therapeutic target for the treatment of obesity and obesity-related diseases.PRDM16 is a master transcriptional coregulator in brown adipocytes. It forms complexes with various transcriptional cofactors in a promoter-dependent context, acting bifunctionally to promote expression of brown fat-selective genes and repress white-selective genes.PRDM16 also regulates hematopoietic and neural stem cell maintenance, patalogenesis, and cardiac development. Disruption in PRDM16 function affects cardiac development and leukemogenesis in humans.