Figure 4: Multivalent HP1α-chromatin interactions increase association speed.
From: Multivalency governs HP1α association dynamics with the silent chromatin state
(a) Distribution of interaction kinetics from HP1α with single chromatin arrays: Two dimensional histograms of single-array binding kinetics showing the correlation of dissociation time constants, τoff,1 and τoff,2 with the apparent association time constant λon. (b) Two dimensional histogram of single-array binding kinetics for HP1αcdm. (c) Comparison of the average dissociation time constants τoff,1 and τoff,2 (fast and slow phase) between HP1α and HP1αcdm (errors: s.e.m., n=4–16 replicates, *P<0.05, Student's t-test). (d) Comparison of the association rate constant kon between HP1α and HP1αcdm (errors: s.e.m., n=4–16 replicates, *P<0.05, Student's t-test). (c,d) For all fit results, see Table 1. (e) Brownian dynamics simulation of chromatin binding: monomeric or dimeric binders are diffusing in a box with 200 nm edge length containing a 12-nucleosome chromatin array. First passage binding kinetics are plotted for monomeric (red) and dimeric (green) binders at 20 and 10 μM binder concentration, respectively. Single-exponential fits yield λon=53.6 τD for the dimeric and λon=89 τD for the monomeric binder (τD is the characteristic diffusion time, τD=6πηa3/(kBT) for binders with radius a in solvent with viscosity η, kBT being the thermal energy). (f) Kinetic model for chromatin binding of HP1α: HP1α in a monomer-dimer equilibrium (kmono, kdim) associates nonspecifically (kassoc) and reversibly (kdissoc) with nucleosomes (short-lived interactions with (i) the nucleosomal or linker DNA, (ii) the nucleosomal surface or (iii) different regions on histone tails) before transitioning to a specific, H3K9me3 bound state (kbind) with a 100 ms-residence time (krelease). The nonspecific association of dimeric protein is prolonged by a factor α, and it can further proceed to a bivalent state (kbiv). (g) Comparison of experimental data of HP1α and HP1αcdm chromatin binding with results from kinetic model in (f). For parameters, see Supplementary Table 1.
