Fig. 8

Hierarchical dynamics revealed by MSM analysis of the MISA network in the slow DNA-binding/unbinding parameter regime. All network parameters listed in Additional file 1: Table S1. a Eigenvalue spectrum of T(τ), τ = 1, showing 16 dominant eigenvalues. b 4-macrostate MSM: 70% probability contours superimposed onto the quasipotential surface. In this parameter regime, separate attractors in the landscape are kinetically linked in the same subnetwork (see text). c 16-macrostate MSM showing 4 highly connected subnetworks (colored ovals). Each macrostate corresponds to a particular promoter binding-configuration (see numbering scheme in Additional file 1: Table S5). A pair of representative transition paths through the network are highlighted. Red path: most probable forward transition path from macrostate 1 to macrostate 11. Blue path: most probable reverse path from 11 to 1. d State transition graph for the 4-macrostate MSM. e Brute force SSA simulation of the MISA network over time. Trajectory is plotted according to the 16-macrostate (promoter configuration) indexing as in panel C and Additional file 1: Table S5. Colored panels reflect the four subnetworks/C = 4 macrostates. Orange inset: zoomed in trajectory segment, showing a switching event between the red and green subnetworks