TY - JOUR T1 - Super-resolution Imaging Reveals 3D Structure and Organizing Mechanism of Accessible Chromatin JF - bioRxiv DO - 10.1101/678649 SP - 678649 AU - Liangqi Xie AU - Peng Dong AU - Yifeng Qi AU - Margherita De Marzio AU - Xingqi Chen AU - Sambashiva Banala AU - Wesley R. Legant AU - Brian P. English AU - Anders S. Hansen AU - Anton Schulmann AU - Luke D. Lavis AU - Eric Betzig AU - Rafael Casellas AU - Howard Y. Chang AU - Bin Zhang AU - Robert Tjian AU - Zhe Liu Y1 - 2019/01/01 UR - http://biorxiv.org/content/early/2019/06/21/678649.abstract N2 - 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 intrachromosomal 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. ER -