PRDM16

PRDM16, or PR domain containing 16, is a transcriptional regulator in the PRDM family. The encoded protein features an N-terminal PR domain and several C2H2 zinc finger motifs at the C-terminus, enabling interactions with chromatin and DNA. The PR domain is related to histone methyltransferase activity in the family and may mediate protein–protein interactions, while the zinc fingers support sequence-specific DNA binding and transcriptional control. The precise enzymatic activity of PRDM16 remains a topic of research, but it is widely recognized as a key regulator of gene expression programs.

A central role of PRDM16 is in brown adipose tissue (BAT) development and thermogenesis. In adipocyte precursors, PRDM16 acts as a transcriptional switch that promotes brown fat lineage and suppresses myogenic programs. It cooperates with C/EBP-β and PGC-1α to activate a brown-fat gene program, including UCP1. Experimental overexpression can induce brown-fat–like characteristics in white fat, while loss of PRDM16 impairs BAT formation.

In addition to adipose tissue, PRDM16 influences hematopoietic stem cell maintenance and lineage decisions. It is involved in regulating self-renewal and differentiation of hematopoietic progenitors, though the detailed mechanisms are still being explored.

Genetic alterations involving PRDM16 have been linked to hematologic malignancies. Chromosomal rearrangements can generate PRDM16-related fusion genes that are associated with acute myeloid leukemia and related disorders, indicating that dysregulated PRDM16 activity can contribute to disease.

PRDM16 is broadly expressed across tissues and is subject to regulation by signaling pathways that influence adipogenesis, metabolism, and development. Ongoing research aims to clarify its exact enzymatic activities, interaction partners, and broader roles in health and disease.