In colon epithelium, the expression level of KLF4 is duodenum > jejunum > ileum，that is consistent with differentiation and proliferation of intestinal epithelial cells. Meanwhile, KLF4 and proliferating cell nuclear antigen (PCNA) showed a reciprocal pattern of expression.
Wnt signaling plays an important role in homeostasis and transformation of the intestinal mucosa through its regulation of both proliferation and cell differentiation. Tcf4, which is a principal effecter of Wnt signaling, shows a complete loss of proliferating cells in the intestinal crypt with terminal differentiation of the epithelial cells. Further, Wnt signaling is also involved in controlling secretary cell differentiation. There are cross talks of KLF4 and Wnt signaling pathway.
- TCF4 and Sox9 control the expression of KLF4
In the 4.0 kb upstream of the KLF4 transcription start site do not find a canonical TCF binding sequence (AAGATCAAAGGG), TCF4 down regulates KLF4 expression may not have depended on direct interaction with the KLF4 promoter. However, SOX9 is modulated by TCF4 and in turn represses the differentiation markers. In factor, SOX9 is the intermediate between KLF4 and TCF4, which can inhibit the expression of KLF4 by directly binding to the promoter. So, SOX9 is directly regulated by Wnt signaling, it is a candidate for the bridge between Wnt/TCF4 signaling and down-regulation of KLF4 in proliferation and differentiation.