Inhibition of Tcf3 binding by I-mfa domain proteins

We have determined that I-mfa, an inhibitor of several basic helix-loop-hel ix (bHLB) proteins, and XIC, a Xenopus ortholog of human I-mf domain-contai ning protein that shares a highly conserved cysteine-rich C-terminal domain with I-mfa, inhibit the activity and DNA binding of the HMG box transcript ion factor XTcf3. Ectopic expression of I-mfa or XIC in early Xenopus embry os inhibited dorsal axis specification, the expression of the Tcf3/beta -ca tenin-regulated genes siamois and Xnr3, and the ability of beta -catenin to activate reporter constructs driven by Lef/Tcf binding sites. I-mfa domain proteins can regulate both the Wnt signaling pathway and a subset of bHLH proteins, possibly coordinating the activities of these two critical develo pmental pathways.