The beta-catenin/VegT-regulated early zygotic gene Xnr5 is a direct target of SOX3 regulation.

In Xenopus laevis, beta-catenin-mediated dorsal axis formation can be suppressed by overexpression of the HMG-box transcription factor XSOX3. Mutational analysis indicates that this effect is due not to the binding of XSOX3 to beta-catenin nor to its competition with beta-catenin-regulated TCF-type transcription factors for specific DNA binding sites, but rather to SOX3 binding to sites within the promoter of the early VegT- and beta-catenin-regulated dorsal-mesoderm-inducing gene Xnr5. Although B1-type SOX proteins, such as XSOX3, are commonly thought to act as transcriptional activators, XSOX3 acts as a transcriptional repressor of Xnr5 in both the intact embryo and animal caps injected with VegT RNA. Expression of a chimeric polypeptide composed of XSOX3 and a VP16 transcriptional activation domain or morpholino-induced decrease in endogenous XSOX3 polypeptide levels lead to an increase in Xnr5 expression, as does injection of an anti-XSOX3 antibody that inhibits XSOX3 DNA binding. These observations indicate that maternal XSOX3 acts in a novel manner to restrict Xnr5 expression to the vegetal hemisphere.