Auto-regulation of human Tcf-4 by Wnt-β-catenin-Tcf-4 signaling

Aims: Tcf-4 is a major transcription factor in the Wnt/β-catenin pathway. Wnt signaling plays a critical role in stem cell maintenance and Paneth cell differentiation in intestinal crypts abd over-activation is thought to be important in intestinal carcinogenesis. We recently reported a reduced expression of Tcf-4 in ileal Crohn's disease (CD) leading to reduced expression of Paneth cell α-defensins. This link provides a new mechanism for small intestinal CD pathogenesis. In this study, we aimed to investigate possible Tcf-4 auto-regulation and feedback mechanisms. Methods: Potential Tcf-4 binding sites were ana…