PR domain-containing protein 16 (PRDM16) (PRDM16)

PR domain-containing protein 16 (PRDM16) is a zinc-finger transcription factor that serves as a master regulator of the thermogenic gene program, specifically controlling the differentiation and functional identity of brown and beige adipocytes (UniProt Q9HAZ2; Seale et al., 2008). It functions as a molecular switch, activating mitochondrial and thermogenic genes like UCP1 while simultaneously repressing myogenic and white adipocyte-specific pathways through interactions with co-regulators such as PGC-1alpha and CtBP (NCBI Gene 63976; Cohen et al., 2014). Beyond its metabolic role, PRDM16 is essential for the maintenance of hematopoietic stem cells and the structural integrity of the heart (Bjork et al., 2011). Mutations or dysregulation of the PRDM16 gene are associated with metabolic disorders, dilated cardiomyopathy, and certain forms of leukemia, such as acute myeloid leukemia (UniProt Q9HAZ2; Bjork et al., 2011). While there are currently no FDA-approved drugs directly targeting PRDM16, it is a high-interest target for metabolic and oncological research, with experimental approaches exploring the use of antisense oligonucleotides or small molecules to modulate its expression or activity (Cohen et al., 2014). The targeting of PRDM16 mRNA specifically allows for the modulation of protein levels to either enhance energy expenditure in obesity or reduce oncogenic signaling in cancer.

Other names

MEL1PFM13CMD1LLKMD1LLMDS1/EVI1-like gene 1PR domain-containing protein 16

Modulation of gene expression through recruitment of co-activators or co-repressors and intrinsic histone methyltransferase activity to regulate cell fate and metabolic programs.