A spatially resolved stochastic model reveals the role of supercoiling in transcription regulation
Fig 2
Cooperation of RNAP transcription is favored by high initiation rates and antagonized by low initiation rates.
(A) The apparent RNAP elongation rate increases and reaches maxima (blue shaded region) as the initiation rate increases. Error bars are standard deviations from 1000 simulations. (B) Pearson correlation coefficient of adjacent RNAP trajectories increases and approaches unity (blue shaded region) as the initiation rate increases. The correlation coefficient is normalized such that “0” corresponds to the case of independently transcribing RNAP trajectories and “1” corresponds to the case of the co-transcribing RNAP trajectories in the highest expressed gene. The unnormalized curve is in S4 Fig. (C) The mean distance (dots in boxes) between neighboring RNAP molecules decreases as the initiation rate increases. When the maximal cooperation is reached (intersect with blue shaded region, initiate rate at which maximal elongation rate is reached) the distance is ~ 500 bp. Box borders indicate first and third quartiles of the data, vertical lines standard deviations, and horizontal lines in the box media. (D) Stacked histograms of supercoil density upstream (top), downstream (middle) and torque (bottom) RNAP molecules face during transcription. Supercoil densities of processive and stalled RNAP molecules are shown in green and red, respectively. The torque value above the stall threshold is shaded in grey. (E) Representative kymographs of RNAP translocation trajectories (black lines) with the corresponding supercoiling density (positive in orange and negative in blue) in its vicinity. A time interval of 750–950 s was chosen to maintain a constant mean mRNA copy number at a steady-state under each condition (S3 Fig). The slope of the trajectory reflects the elongation speed of the associated RNAP molecule. Left and right white dashed lines indicate the start and end positions of the transcribing region, respectively. The asteroid in the left kymograph indicates that a slow-moving RNAP molecule started to move with a higher speed after a new RNAP molecule is loaded at the promoter on the left. The arrowhead in the middle kymograph indicates a transcribing RNAP molecule drastically reduces its elongation speed after the leading RNAP (right) terminates its transcription and dissociates.