Fig. 7. Proposed model of ETV2 function in activation of Shh expression. ETV2 functions in multiple steps of gene activation related to limb development.

ETV2 depicted as an orange hexagon: (i) targets nucleosome-occupied regions and mediates nucleosome displacement; (ii) recruits additional transcription factors to the limb enhancers, including the ZRS, and facilitates transcription. ETV2 also (iii) activates transcription as a transcriptional activator. The dosage of ETV2 at the ZRS affects the expression levels and the domain of Shh expression and leads to polydactyly.