Transcription-induced active forces suppress chromatin motion

Abstract

The organization of interphase chromosomes in a number of species is starting to emerge thanks to advances in a variety of experimental techniques. However, much less is known about the dynamics, especially in the functional states of chromatin. Some experiments have shown that the mobility of individual loci in human interphase chromosome decreases during transcription, and increases upon inhibiting transcription. This is a counter-intuitive finding because it is thought that the active mechanical force (F) on the order of ten pico-newtons, generated by RNA polymerase II (RNAPII) that is pre-sumably transmitted to the gene-rich region of the chromatin, would render it more open, thus enhancing the mobility. Inspired by these observations, we developed a minimal active copolymer model for interphase chromosomes to investigate how F affects the dynamical properties of chromatin. The movements of the loci in the gene-rich region are suppressed in an intermediate range of F, and are enhanced at small F values, which has also been observed in experiments. In the intermediate F, the bond length between consecutive loci increases, becoming commensurate with the distance at the minimum of the attractive interaction between non-bonded loci. This results in a transient disorder-to-order transition, leading to the decreased mobility during transcription. Strikingly, the F -dependent change in the locus dynamics preserves the organization of the chromosome at F = 0. Transient ordering of the loci, which is not found in the polymers with random epigenetic profiles, in the gene-rich region might be a plausible mechanism for nucleating a dynamic network involving transcription factors, RNAPII, and chromatin. Significance StatementIn order to explain a physically counter-intuitive experimental finding that chromatin mobility is reduced during transcription, we introduced a polymer model for interphase chromosome that accounts for RNA polymerase (RNAP) induced active force. The simulations show that, over a range of active forces, the mobility of the gene-rich loci is suppressed. Outside this range, chromosomes are compact and exhibit glass-like dynamics. Our study, which accounts for the experimental observations, leads to a novel and testable mechanism of how transcription could shape the coexistence of fluid- and solid-like properties within chromosomes.