RT Journal Article
SR Electronic
T1 Super-resolution Imaging Reveals 3D Structure and Organizing Mechanism of Accessible Chromatin
JF bioRxiv
FD Cold Spring Harbor Laboratory
SP 678649
DO 10.1101/678649
A1 Xie, Liangqi
A1 Dong, Peng
A1 Qi, Yifeng
A1 De Marzio, Margherita
A1 Chen, Xingqi
A1 Banala, Sambashiva
A1 Legant, Wesley R.
A1 English, Brian P.
A1 Hansen, Anders S.
A1 Schulmann, Anton
A1 Lavis, Luke D.
A1 Betzig, Eric
A1 Casellas, Rafael
A1 Chang, Howard Y.
A1 Zhang, Bin
A1 Tjian, Robert
A1 Liu, Zhe
YR 2019
UL http://biorxiv.org/content/early/2019/06/21/678649.abstract
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.