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

Liangqi Xie, Peng Dong, Yifeng Qi, Margherita De Marzio, Xingqi Chen, Sambashiva Banala, Wesley R. Legant, Brian P. English, Anders S. Hansen, Anton Schulmann, Luke D. Lavis, Eric Betzig, Rafael Casellas, Howard Y. Chang, Bin Zhang, Robert Tjian, Zhe Liu
doi: https://doi.org/10.1101/678649
Liangqi Xie
2Department of Molecular and Cell Biology, Li Ka Shing Center for Biomedical and Health Sciences, CIRM Center of Excellence, University of California, Berkeley, CA 94720, USA
3Howard Hughes Medical Institute, Berkeley, CA 94720, USA
6Janelia Visitor Program, Janelia Research Campus, Ashburn, VA 20147, USA
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Peng Dong
1Janelia Research Campus, Howard Hughes Medical Institute, Ashburn, VA 20147, USA
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Yifeng Qi
4Departments of Chemistry, Massachusetts Institute of Technology, 77 Massachusetts Ave, Cambridge, MA 02139-4307, USA
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Margherita De Marzio
4Departments of Chemistry, Massachusetts Institute of Technology, 77 Massachusetts Ave, Cambridge, MA 02139-4307, USA
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Xingqi Chen
5Center for Personal Dynamic Regulomes and Howard Hughes Medical Institute, Stanford University, Stanford, CA 94305, USA
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Sambashiva Banala
3Howard Hughes Medical Institute, Berkeley, CA 94720, USA
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Wesley R. Legant
1Janelia Research Campus, Howard Hughes Medical Institute, Ashburn, VA 20147, USA
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Brian P. English
1Janelia Research Campus, Howard Hughes Medical Institute, Ashburn, VA 20147, USA
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Anders S. Hansen
2Department of Molecular and Cell Biology, Li Ka Shing Center for Biomedical and Health Sciences, CIRM Center of Excellence, University of California, Berkeley, CA 94720, USA
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Anton Schulmann
1Janelia Research Campus, Howard Hughes Medical Institute, Ashburn, VA 20147, USA
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Luke D. Lavis
1Janelia Research Campus, Howard Hughes Medical Institute, Ashburn, VA 20147, USA
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Eric Betzig
1Janelia Research Campus, Howard Hughes Medical Institute, Ashburn, VA 20147, USA
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Rafael Casellas
7Lymphocyte Nuclear Biology, NIAMS and Center of Cancer Research, NCI, NIH, Bethesda, MD 20892, USA
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Howard Y. Chang
5Center for Personal Dynamic Regulomes and Howard Hughes Medical Institute, Stanford University, Stanford, CA 94305, USA
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Bin Zhang
4Departments of Chemistry, Massachusetts Institute of Technology, 77 Massachusetts Ave, Cambridge, MA 02139-4307, USA
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  • For correspondence: liuz11@janelia.hhmi.org jmlim@berkeley.edu binz@mit.edu
Robert Tjian
2Department of Molecular and Cell Biology, Li Ka Shing Center for Biomedical and Health Sciences, CIRM Center of Excellence, University of California, Berkeley, CA 94720, USA
3Howard Hughes Medical Institute, Berkeley, CA 94720, USA
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  • For correspondence: liuz11@janelia.hhmi.org jmlim@berkeley.edu binz@mit.edu
Zhe Liu
1Janelia Research Campus, Howard Hughes Medical Institute, Ashburn, VA 20147, USA
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  • For correspondence: liuz11@janelia.hhmi.org jmlim@berkeley.edu binz@mit.edu
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Abstract

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.

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  • ↵† Co-first author

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Posted June 21, 2019.
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Super-resolution Imaging Reveals 3D Structure and Organizing Mechanism of Accessible Chromatin
Liangqi Xie, Peng Dong, Yifeng Qi, Margherita De Marzio, Xingqi Chen, Sambashiva Banala, Wesley R. Legant, Brian P. English, Anders S. Hansen, Anton Schulmann, Luke D. Lavis, Eric Betzig, Rafael Casellas, Howard Y. Chang, Bin Zhang, Robert Tjian, Zhe Liu
bioRxiv 678649; doi: https://doi.org/10.1101/678649
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Super-resolution Imaging Reveals 3D Structure and Organizing Mechanism of Accessible Chromatin
Liangqi Xie, Peng Dong, Yifeng Qi, Margherita De Marzio, Xingqi Chen, Sambashiva Banala, Wesley R. Legant, Brian P. English, Anders S. Hansen, Anton Schulmann, Luke D. Lavis, Eric Betzig, Rafael Casellas, Howard Y. Chang, Bin Zhang, Robert Tjian, Zhe Liu
bioRxiv 678649; doi: https://doi.org/10.1101/678649

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