Individual transcription factors modulate both the micromovement of chromatin and its long- range structure

• 成果类型: Article
• 署名作者: Shaban, Haitham A.; Friman, Elias T.; Deluz, Cedric; Tollenaere, Armelle; Katanayeva, Natalya; Suter, David M.
• 署名单位: Swiss School of Public Health (SSPH+); Swiss Federal Institutes of Technology Domain; Ecole Polytechnique Federale de Lausanne; Egyptian Knowledge Bank (EKB); National Research Centre (NRC); UK Research & Innovation (UKRI); Medical Research Council UK (MRC); University of Edinburgh; Swiss Federal Institutes of Technology Domain; Ecole Polytechnique Federale de Lausanne; Swiss Institute Experimental Cancer Research; Swiss School of Public Health (SSPH+); University of Geneva
• 刊物名称: PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
• ISSN/ISSBN: 0027-14922
• DOI: 10.1073/pnas.2311374121
• 发表日期: 2024-04-30
• 关键词: dynamics; ORGANIZATION; genome; cdx2; determines; diffusion; proteins; mobility; SYSTEM; fate

摘要

The control of eukaryotic gene expression is intimately connected to highly dynamic chromatin structures. Gene regulation relies on activator and repressor transcription factors (TFs) that induce local chromatin opening and closing. However, it is unclear how nucleuswide chromatin organization responds dynamically to the activity of specific TFs. Here, we examined how two TFs with opposite effects on local chromatin accessibility modulate chromatin dynamics nucleuswide. We combine high - resolution diffusion mapping and dense flow reconstruction and correlation in living cells 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 the expression of either an individual transcriptional activator (CDX2) or repressor (SIX6) with large numbers of binding sites increases chromatin mobility nucleuswide, yet they induce opposite coherent chromatin motions at the micron scale. Hi - C analysis of higher - order chromatin structures shows that induction of the pioneer factor CDX2 leads both to changes in local chromatin interactions and the distribution of A and B compartments, thus relating the micromovement of chromatin with changes in compartmental structures. Given that inhibition of transcription initiation and elongation by RNA Pol II has a partial impact on the global chromatin dynamics induced by CDX2, we suggest that CDX2 overexpression alters chromatin structure dynamics both dependently and independently of transcription. Our biophysical analysis shows that sequence - specific TFs can influence chromatin structure on multiple architectural levels, arguing that local chromatin changes brought by TFs alter long - range chromatin mobility and its organization.