Super-resolution Imaging Reveals 3D Structure and Organizing Mechanism of Accessible Chromatin [article]

Liangqi Xie, Peng Dong, Yifeng Qi, Margherita De Marzio, Xingqi Chen, Sambashiva Banala, Wesley R Legant, Brian P English, Anders Hansen, Anton Schulmann, Luke D Lavis, Eric Betzig (+5 others)
2019 bioRxiv   pre-print
Access to cis-regulatory elements packaged in chromatin is essential for directing gene expression and cell viability. Here, we report a super-resolution imaging strategy, 3D ATAC-PALM, that enables direct visualization of the entire accessible genome. We found that active chromosomal segments are organized into spatially-segregated accessible chromatin domains (ACDs). Rapid depletion of CTCF or Cohesin (RAD21 subunit) induced enhanced ACD clustering, reduced physical separation between
more » ... omosomal ACDs, and differentially regulated ACD compaction. Experimental perturbations and polymer modeling suggest that dynamic protein-protein and protein-DNA interactions within ACDs couple with loop extrusion to organize ACD topology. Dysorganization of ACDs upon CTCF or Cohesin loss alters transcription factor binding and target search dynamics in living cells. These results uncover fundamental mechanisms underpinning the formation of 3D genome architecture and its pivotal function in transcriptional regulation.
doi:10.1101/678649 fatcat:isascfdol5cbbmq46bnyvm7hii