The SoxD transcription factors – Sox5, Sox6, and Sox13 – are key cell fate modulators

Sox5, Sox6, and Sox13 constitute the group D of sex-determining region (Sry)-related transcription factors. They are highly conserved in the family-specific high-mobility-group (HMG) box DNA-binding domain and in a group-specific coiled-coil domain. The latter mediates SoxD protein dimerization and thereby preferential binding to pairs of DNA recognition sites. The SoxD genes have overlapping expression and cell-autonomously control discrete lineages. Sox5 and Sox6 redundantly enhance chondrogenesis, but retard gliogenesis. Sox5 hinders melanogenesis, promotes neural crest generation, and controls the pace of neurogenesis. Sox6 promotes erythropoiesis, and Sox13 modulates T cell specification and is an autoimmune antigen. SoxD proteins enhance transactivation by Sox9 in chondrocytes, but antagonize Sox9 and other SoxE proteins in oligodendrocytes and melanocytes, and also repress transcription through various mechanisms in several other lineages. While their biological and molecular functions remain incompletely understood, the SoxD proteins have thus already proven that they critically modulate cell fate in major lineages.