Figure 7. Schematic representation of the relationship between sequence divergence and TF occupancy on enhancer elements.
Upper panel, indicates an enhancer bound directly by two factors, A and B. In some enhancers the loss of TF binding (e.g. TF B) is associated with the loss of that TF’s binding site (motif b - middle). In other enhancers (right), the loss of a partner TF’s motif (motif a) will result in the loss of binding of TF B, indicating that TF B occupies the enhancer cooperatively (either directly or indirectly) with TF A. Both cases have been observed in inter- and intra- species analysis of TF occupancy, and are also observed here with these mesodermal developmental TFs. Lower panel, represents an enhancer bound by a TF collective. Here, the loss of motif b does not result in loss of TF B binding (middle panel), unlike the situation in enhancers with purely additive occupancy (depicted above). Rather the divergence in the TF binding site is tolerated as the TF’s binding is stabilized through protein-protein interactions.