A transcriptional cycling model recapitulates chromatin-dependent features of noisy inducible transcription
Fig 5
The three-state transcriptional cycling model reproduces transcriptional activation heterogeneity observed for a range of latent HIV integrations.
(A) Ratio of enrichment of total histone H3 to acetylated H3 (AcH3) in Jurkat T cells at the indicated target promoters quantified by ChIP-qPCR. Data are presented as mean of % input (non-IP control) ± SD of two biological replicates. (B) Experimental GFP-HIV trajectories for the four HIV integrations, plotted with 95% confidence intervals and normalized via experimental setup. (C-E) Scatterplots of three-state promoter simulation with feedback compared to experimental measurements for mRNA Average (C), Fano factor (D), and CV (E). Error bars represent 95% bootstrapped confidence intervals (C) Fractional state probabilities under basal conditions of UP (blue), AP (teal) and BP (yellow) for the four integrations based upon the three-state model. Simulations were run 10,000 times. (F) Representative simulated protein trajectories over 24 hours of the 4 integrations. (G) Violin kernel fitting of protein distributions at basal conditions and at 24 hours of the four integrations. Black bar represents mean. Red dashed line represents a protein threshold of 275 with percentages as the amount above that threshold. Experimental data in this figure reproduced from [4].