Fig. 2.

Emerging complexities in Wnt target gene regulation covered in this mini-review. A) As described by Franz et al, many Wnt target genes show no evidence of TCF/Pan dependent repression in the absence of Wnt signaling.^[54] B) Model proposed in vanTienen et al, where in the absence of Wnt signaling, TLE, BCL9/B9L and Pygo proteins co-occupy W-CRMs.^[60] C) This model postulated that these factors are also associated with TCF in Wnt-stimulated cells, along with β-catenin and other co-activators. There is also evidence that TLEs are inactivated by ubiquitylation via UBR5 (not shown).^[42] In addition, newly discovered negative regulatory elements (NREs) are proposed to be bound by TCFs and β-catenin, repressing transcription upon Wnt stimulation, fine-tuning the transcriptional response of traditional W-CRMs.^[76] Each of these models have important considerations. The work of Franz et al is limited to a single Drosophila cell line, while the “TCF complex reconfiguration” model of vanTienen et al is based on complex composition in solution, not on W-CRM chromatin. The extent of UBR5 modification of TLEs, while evolutionarily conserved, requires further study, as does the functional importance of NREs in regulating Wnt targets. See text for further comment.