Model simulation of the perturbation of chromatin dynamics after trichostatin A (TSA) treatment. (A) Effects of TSA-treatment kinetics on the mCherry fluorescence distributions for two cellular clones, C5 (red) and C11 (blue) measured by flow cytometry. (B) New chromatin dynamics (mean burst size (ρ/koff) and mean closed time (1/kon)) fitting the observed fluorescence distribution evolution induced by TSA treatment. Different examples of these chromatin dynamics, inducing a higher open mean time (resulting from TSA treatment), are illustrated in the detailed view. After distribution-comparison tests, the best new chromatin dynamics (green), and those related to the steady state (brown) were ascertained. min, minutes; h, hours; d, days. (C) Simulated mCherry fluorescence distribution evolution obtained for the best new chromatin dynamics (see panel (B)). (Insets) Evolutions of the distribution-comparison scores (comparisons between measured distributions after TSA treatment and the simulated distributions). (D) One run of the Gillespie SSA per clone showing the dynamics of the chromatin before and during 48 hours of TSA treatment (opening and closing chromatin events are shown in black) for one virtual cell of the isogenic population distributions (see panel (C)). Consequences of chromatin open/closed dynamics on mRNA transcription and protein translation are shown in blue and in red respectively. Production (+) and degradation (-) evolutions of mRNAs and proteins are also shown. The beginning of TSA treatment is indicated by a vertical blue line. (For illustration, Figure S3 (see Additional file 5) shows the same analysis as presented in this figure but for a parameter set (same as used in Additional file 3, Figure S2) showing a weaker fit).
Viñuelas et al. BMC Biology 2013 11:15 doi:10.1186/1741-7007-11-15