Coevolution of HMG domains and homeodomains and the generation of transcriptional regulation by Sox/POU complexes

Abstract

The highly conserved homeodomains and HMG domains are components of a large number of proteins that play a role in the transcriptional regulation of gene expression during embryogenesis. Both the HMG domain and the homeodomain serve as interfaces for factor interactions with DNA, as well as with other proteins, and it is likely that the high degree of structural and sequence conservation within these domains reflects the conservation of basic aspects of these interactions. Classical HMG domain proteins have an ancient origin, being found in all eukaryotes, and are thought to have given rise to the metazoan-specific class of HMG domain proteins called the Sox proteins. Similarly, the metazoan-specific POU domain proteins are thought to have arisen from genes encoding ancestral homeodomain proteins. In this review, we summarize several examples of different HMG-homeodomain interactions that illustrate not only the ancient origin of each of these protein families, but also their relationship to each other, and discuss how coevolution of HMG and homeodomains may have lead to creation of the specialized Sox/POU protein complexes. Using the FGF-4 gene as an example, we also speculate on how coevolution of regulatory Sox/POU target DNA sequences may have occurred, and how the summation of these changes may have lead to the emergence of new developmental pathways.

Sox2 signaling in prosensory domain specification and subsequent hair cell differentiation in the developing cochlea

“…Additional work to identify other molecular components of the Sox2 pathway should identify crucial co-factors (20,21) that determine the different molecular effects of Sox2 in different cells and at different developmental time points during inner ear development. In addition to the upstream Notch signaling that we describe, it would be interesting to investigate whether Wnt and/or FGF signaling, both known to play early roles in inner ear development (22)(23)(24), also converge to activate Sox2 expression as they do in developing neural plate (25).…”

Ube2s regulates Sox2 stability and mouse ES cell maintenance

“…[38][39][40][41] At the molecular level, Sox2 serves as a pioneer factor and is involved in cell fate determination through its dynamic interactions with different protein partners for transcriptional regulation of corresponding sets of target genes. [42][43][44][45] For example, in undifferentiated ES cells, Sox2 forms a heterodimer with Oct4 to activate stemness-related genes while repressing differentiationspecific genes. 2,25 Upon ES cell differentiation, their interaction is disturbed.…”

Oct4 and Sox2 overexpression improves the proliferation and differentiation of bone mesenchymal stem cells in Xiaomeishan porcine

“…Oct4 and Sox2 are transcription factors known to be essential for normal pluripotent cell development and maintenance (Dailey and Basilico, 2001;Rodda et al, 2005). Oct4 is a critical transcription factor for regulating self-renewal and differentiation of ESCs.…”