Fig. S7.
Model of the feedback and feed-forward mechanisms that regulate of the Hand1PA/OFT enhancer. In this model, the H1 expression domain (blue) represents the distal cap domain of MD1. H1 trans activation depends on BMP signaling (green) via SMAD factors, H2 (dark red), and GATA2/3 (purple) through direct DNA binding. EDN1 is initially required for Bmp ligand up-regulation and, via DLX5/6 up-regulation (yellow), is directly necessary for H2 PA expression. BMP and H2 transcriptional activity overlaps where H1 is expressed, and this overlap defines the distal cap. Within the proximal arch, DLX5/6 directly antagonize Hand1 transcriptional activity via disruption of BMP, H2, and GATA transcriptional inputs. Increasing BMP signaling expands the distal cap domain increasing the proximal border of H1 and restricting the distal border of Dlx5/6.