title: Cellular-automaton model of the cooperative dynamics of RNA polymerase II during transcription in human cells.
abstract: RNA polymerase II (RNAPII) is the responsible motor protein for transcription. Here we report the formulation and results of a cellular automaton model of the RNAPII dynamics of gene transcription that takes account the effect of the velocity change according to the gene position, such as occurs in introns and exons. We describe RNAPII dynamics in terms of the properties in the time domain, such as elapsed time, residence time, and time intervals. We found that the RNAPII molecules move as a free-flow state, though regions of reduced velocity do exist such as exons, as far as the time interval between nearest RNAPII molecules is larger than the time required for an RNAPII passing the exclusion length in the velocity reduction region. On the other hand, if the reduction is strong enough to reach a certain threshold, at the maximally reductive velocity region, a transition occurs from the RNAPII free-flow state to the states with congested and repetitive flows. We analytically obtained the conditions for these flow states and the transition threshold. From simulations of high-density RNAPII in the SAMD4A gene with the strong blockade, we confirmed the transition from free flow to the repetitive and congested flows, suggesting that the transition may serve as a regulatory mechanism of gene expression. By fitting the experimentally observed RNAPII density profile of the SAMD4A gene during the course of transcription of the normal and altered gene (in knock-down cells) with or without roadblock, we found that the RNAPII density flow is a free state. However, even in this free state, there is a long-range correlation between RNAPII molecules, ranging from 1 to 20 min, with the corresponding distance from 3 to 80 kbp, during transcription in normal cells. This long-range correlation probably relates to the higher-order DNA loop structure.
authors.affiliation: Research Center for Advanced Science and Technology, University of Tokyo, Tokyo 153-8904, Japan.
authors.forename: Yoshihiro
authors.initials: Y
authors.lastname: Ohta
authors.forename: Tatsuhiko
authors.initials: T
authors.lastname: Kodama
authors.forename: Sigeo
authors.initials: S
authors.lastname: Ihara
mesh_terms: D003198:Computer Simulation; D006801:Humans; D008957:Models, Genetic; D012319:RNA Polymerase II / Q000235:genetics*; D014158:Transcription, Genetic / Q000235:genetics*; D015533:Transcriptional Activation
chemical_list: D012319:RNA Polymerase II