PT  - JOURNAL ARTICLE
AU  - Xie, Liangqi
AU  - Dong, Peng
AU  - Qi, Yifeng
AU  - De Marzio, Margherita
AU  - Chen, Xingqi
AU  - Banala, Sambashiva
AU  - Legant, Wesley R.
AU  - English, Brian P.
AU  - Hansen, Anders S.
AU  - Schulmann, Anton
AU  - Lavis, Luke D.
AU  - Betzig, Eric
AU  - Casellas, Rafael
AU  - Chang, Howard Y.
AU  - Zhang, Bin
AU  - Tjian, Robert
AU  - Liu, Zhe
TI  - Super-resolution Imaging Reveals 3D Structure and Organizing Mechanism of Accessible Chromatin
AID  - 10.1101/678649
DP  - 2019 Jan 01
TA  - bioRxiv
PG  - 678649
4099  - http://biorxiv.org/content/early/2019/06/21/678649.short
4100  - http://biorxiv.org/content/early/2019/06/21/678649.full
AB  - 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.