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

Abstract

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.

Figure 1

Schematic of the human SoxD proteins. The coiled-coil dimerization domain and HMG box DNA-binding domain are shown, as well as the amino acid positions at the beginning and end of the proteins and internal domains. Predicted molecular weights are indicated on the right.

Figure 2

Schematic illustrating various modes of action of the SoxD proteins. (A) Sox5 and Sox6 cooperate with Sox9 in transactivating chondrocyte-specific genes. They bind to recognition sites nearby, but distinct from those of Sox9. (B) SoxD proteins repress transcription through various mechanisms. They compete with SoxE proteins in binding to recognition sites on oligodendrocyte- and melanocyte-specific genes, and recruit co-repressors. Sox13 interacts with Tcf1 in T cells, thereby preventing it from binding to target genes. Sox6 blocks expression of embryonic globin genes in erythroid cells by binding to recognition sites in the proximal promoters.