Runtrelated

The runt-related (runt-related) transcription factor family, often abbreviated as RUNX, is a group of evolutionarily conserved transcription factors named for the Drosophila gene runt. In vertebrates these include RUNX1, RUNX2, and RUNX3. The defining feature is the runt homology domain (Runt domain), a DNA-binding region that operates in partnership with the cofactor CBFβ.

RUNX proteins regulate diverse developmental processes across tissues. RUNX1 is essential for definitive hematopoiesis and lymphoid lineage specification; RUNX2 is the master regulator of osteoblast differentiation and skeletal morphogenesis; RUNX3 participates in gastric epithelial development, TGF-β signaling, and neuronal differentiation. They can act as activators or repressors depending on context.

Mechanistically, RUNX proteins bind DNA at specific consensus motifs and function mainly as heterodimers with CBFβ, which increases DNA-binding affinity. They operate within broader transcriptional networks, interacting with SMADs, AP-1, and other transcription factors to coordinate gene expression during development and tissue maintenance.

Clinical relevance: Alterations in RUNX genes underlie human disease. RUNX1 mutations or rearrangements are linked to acute myeloid leukemia and familial platelet disorder. RUNX2 mutations cause cleidocranial dysplasia, a skeletal disorder. RUNX3 expression changes are associated with several cancers, notably gastric cancer, where loss of expression is common.

In research, the runt-related family provides insight into developmental biology, hematology, osteogenesis, and oncology. Ongoing work investigates regulatory networks, partner proteins, and how context determines RUNX function as oncogenes or tumor suppressors.