Individual activator and repressor transcription factors act as modulators of global chromatin mobility.

Abstract

Eukaryotic gene regulation is governed by the spatiotemporal organization of chromatin structures1,2. Alteration in chromatin structures is controlled by activator and repressor transcription factors (TFs) that lead to decreased or increased compaction (chromatin opening and closing, respectively)3-5. While it is known that this activity induces local changes in chromatin mobility, whether larger-scale chromatin structures respond dynamically to the activity of specific TFs remains unclear. Here we asked how TFs with opposite effects on modulating local chromatin accessibility impact nucleus-wide chromatin dynamics in living cells. We combine High-resolution Diffusion mapping (Hi-D)6 and Dense Flow reConstruction and Correlation (DFCC)7,8 to obtain an imaging-based, nanometer-scale analysis of local diffusion processes and long-range coordinated movements of both chromatin and TFs. We show that individual activator and repressor TFs increase nucleus-wide chromatin mobility and induce opposite coherent chromatin motions at the micron scale. Our quantitative analysis thus reveals the broad and differential impact of TFs opening and closing chromatin in nucleus-wide chromatin dynamics. This establishes the impact of TFs in shaping long-range chromatin mobility and provides a biophysical understanding of how global chromatin structure responds dynamically to TFs in living cells.