Fig. 3

ELF3 inhibits EMT induction. A Schematic representation of ELF3 coupled with an EMT regulatory network (dotted rectangle) consisting of miR-200, ZEB1, SNAIL, SLUG and KLF4. Green arrows denote activation, and red bars indicate inhibition. Solid arrows represent transcriptional regulation; dotted lines represent microRNA-mediated regulation. B Bifurcation diagrams for ZEB1/2 mRNA levels in response to an external signal (I_ext) levels for the coupled EMT–ELF3 circuit (solid blue and dotted red curve) and the core EMT circuit (solid green and dotted black curve). Black arrows indicate the region of the hybrid E/M state and red arrows indicate a switch from an epithelial phenotype. C Temporal dynamics of ZEB1/2 mRNA levels in a cell starting in an epithelial phenotype when exposed to a high level of an external EMT signal (I_ext = 100,000 molecules) (green-shaded region) for the circuits shown in panel E. D Schematic representation of the ELF3 network coupled with WT1. Green arrows denote activation, red bars indicate inhibition. E Bifurcation diagrams for ZEB1/2 mRNA levels in response to an external signal (I_ext) levels for the coupled WT1 and coupled ELF3 network (solid pink and dotted black curve), WT1 coupled with the core EMT circuit (no ELF3) (solid yellow and dotted red curve), ELF3 coupled with the core EMT circuit (noWT1) (solid blue and dotted red curve) and core EMT circuit (no ELF3, no WT1) (solid green and dotted black curve). Solid lines indicate the region of the hybrid state; arrows indicate the switch from epithelial phenotype. F Temporal dynamics of ZEB1/2 mRNA levels in a cell starting in an epithelial phenotype when exposed to a high level of an external EMT signal (I_ext = 100,000 molecules) (orange-shaded region) for WT1 and ELF3 coupled with the core EMT network (pink curve), WT1 coupled with the core EMT circuit (no ELF3) (yellow curve), ELF3 coupled with the core EMT circuit (no WT1) (blue curve) and core EMT circuit (no ELF3; no WT1: green curve). G Phase diagrams for WT1 coupled with an ELF3 network driven by an external signal (l_ext) for varying strength of activation from WT1 to SNAIL. H Same as G, but for varying threshold levels along of WT1 to activate SNAIL. I) Same as G, but for varying strength of inhibition of ZEB by ELF3. In G-I, different coloured regions show varied phases (combination of co-existing phenotypes)