7W1M

Cryo-EM structure of human cohesin-CTCF-DNA complex

Summary for 7W1M

• Entry DOI: 10.2210/pdb7w1m/pdb
• EMDB information: 32252
• Descriptor: Structural maintenance of chromosomes protein 1A, BERYLLIUM TRIFLUORIDE ION, ZINC ION, ... (11 entities in total)
• Functional Keywords: cohesin, nipbl, ctcf, dna, chromosome folding, topologically associating domain, chromatin loops, dna loop extrusion, sister chromatid cohesion, complex, atpase, heat repeat protein, dna binding protein, dna binding protein-dna complex, dna binding protein/dna
• Biological source: Homo sapiens (Human); More
• Total number of polymer chains: 8
• Total formula weight: 826702.61

Authors

Shi, Z.B.,Bai, X.C.,Yu, H. (deposition date: 2021-11-19, release date: 2023-05-31, Last modification date: 2023-12-13)

Primary citation

Zhang, H.,Shi, Z.,Banigan, E.J.,Kim, Y.,Yu, H.,Bai, X.C.,Finkelstein, I.J.
CTCF and R-loops are boundaries of cohesin-mediated DNA looping.
Mol.Cell, 83:2856-2871.e8, 2023

PubMed Abstract: Cohesin and CCCTC-binding factor (CTCF) are key regulatory proteins of three-dimensional (3D) genome organization. Cohesin extrudes DNA loops that are anchored by CTCF in a polar orientation. Here, we present direct evidence that CTCF binding polarity controls cohesin-mediated DNA looping. Using single-molecule imaging, we demonstrate that a critical N-terminal motif of CTCF blocks cohesin translocation and DNA looping. The cryo-EM structure of the cohesin-CTCF complex reveals that this CTCF motif ahead of zinc fingers can only reach its binding site on the STAG1 cohesin subunit when the N terminus of CTCF faces cohesin. Remarkably, a C-terminally oriented CTCF accelerates DNA compaction by cohesin. DNA-bound Cas9 and Cas12a ribonucleoproteins are also polar cohesin barriers, indicating that stalling may be intrinsic to cohesin itself. Finally, we show that RNA-DNA hybrids (R-loops) block cohesin-mediated DNA compaction in vitro and are enriched with cohesin subunits in vivo, likely forming TAD boundaries.

PubMed: 37536339
DOI: 10.1016/j.molcel.2023.07.006

Experimental method

ELECTRON MICROSCOPY (6.5 Å)