Figure 7.

Regulation of Stat3 transcriptional activity by DSCR6 and Ezh2 in embryonic patterning. A–D, functional interaction between DSCR6, Ezh2, and Stat3. A, a normal larval stage embryo (stage 40) previously injected with CoMO. B, knockdown of Dscr6 produces anterior deficiency. C, inhibition of Ezh2 phosphorylation by Ezh2-S21A rescues anterior defects in Dscr6 morphants. D, interference with Stat3 lysine methylation by Stat3-K49R rescues anterior defects in Dscr6 morphants. E, a model of functional interaction between DSCR6, Ezh2, and Stat3. Prior to gastrulation, both Ezh2 and Stat3 are phosphorylated and become active. Ezh2 binds to Stat3 and regulates its transcriptional activity through lysine methylation. DSCR6 binds to Ezh2 and Stat3. It may directly interfere with Stat3 transcriptional activity by binding to the C-terminal region that contains protein interaction cassettes and transactivation domain. It may also competitively bind to Ezh2 and interferes with its methyltransferase activity, thus indirectly preventing Stat3 lysine methylation and activation. Scale bar: A–D, 500 μm.