The Multifaceted Roles of PRDM16: Adipose Biology and Beyond

PRDM16 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. 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. 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. or fat cells, are lipid-storing cells that are located within adipose tissue. also termed beiging, refers to the induction of thermogenic gene expression within adipose tissue and adipocytes. enzymes that add acetyl groups to specific lysine residues on a histone protein, allowing transcriptional access to DNA by either neutralizing the positive histone charge or serving as a binding site for chromatin remodeling complexes. enzymes that remove acetyl groups to from specific lysine residues on a histone protein, promoting a more condensed chromatin state and transcriptional gene silencing. enzymes that catalyze the transfer of one, two, or three methyl groups to lysine residues of histone proteins. a large multisubunit coactivator complex that, by acting as a bridge between transcription activators and components of general transcription machinery (RNA polymerase II and general initiation factors), facilitates transcription factor-dependent regulation of gene expression. a protein structural motif composed of around 30 amino acids that are coordinated by at least one zinc ion that mediates sequence-specific binding to DNA.