Role of SoxE transcription factors in development and disease.

Sox8, Sox9, and Sox10 arose by multiple rounds of genome duplications from a single SoxE gene in ancestral vertebrates. In this review, we will briefly discuss the molecular structure and function of SoxE transcription factors and their evolutionary origin. We will then discuss their expression, function, and developmental disorders. SoxE proteins play critical roles during the development of multiple tissues in vertebrate embryos, including the neural crest, inner ear, cartilages, and glia cells of diverse origins, heart, gonads, and gastrointestinal tract. Because they recognize the same DNA sequence, possess conserved functional domains, and have overlapping expression profiles, SoxE proteins act partly redundantly in many contexts. However, Sox8, Sox9, and Sox10 also have many unique and tissue-specific functions. In particular, Sox9 plays an essential role in chondrogenesis, whereas Sox10 is a central regulator of pigment and glia cells. The highly context-specific regulation of different sets of target genes by SoxE factors is due to their ability to interact and cooperate with many other proteins including other transcription factors, cofactors, and enzymes, which modulate their regulatory activity. The activity of SoxE proteins is also frequently altered in a context-dependent fashion by post-translational modifications such as phosphorylation, acetylation, and SUMOylation.