CTCF and R-loops are boundaries of cohesin-mediated DNA looping.

CCCTC-Binding Factor / genetics R-Loop Structures Chromatin Cell Cycle Proteins / genetics DNA / genetics Cohesins
3D genome CTCF R-loop TADs cohesin cryo-EM single-molecule

Journal

Molecular cell
ISSN: 1097-4164
Titre abrégé: Mol Cell
Pays: United States
ID NLM: 9802571

Informations de publication

Date de publication:
17 08 2023
Historique:
received: 21 10 2022
revised: 10 05 2023
accepted: 06 07 2023
medline: 21 8 2023
pubmed: 4 8 2023
entrez: 3 8 2023
Statut: ppublish

Résumé

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.

Identifiants

DOI: 10.1016/j.molcel.2023.07.006 PMID: 37536339
pubmed: 37536339
pii: S1097-2765(23)00520-8
doi: 10.1016/j.molcel.2023.07.006
pii:
doi:

Substances chimiques

CCCTC-Binding Factor 0
Chromatin 0
Cell Cycle Proteins 0
DNA 9007-49-2

Types de publication

Journal Article Research Support, N.I.H., Extramural Research Support, Non-U.S. Gov't

Langues

eng

Sous-ensembles de citation

IM

Pagination

2856-2871.e8

Subventions

Organisme : NHGRI NIH HHS
ID : UM1 HG011536
Pays : United States
Organisme : NIGMS NIH HHS
ID : R01 GM120554
Pays : United States
Organisme : NIGMS NIH HHS
ID : R01 GM143158
Pays : United States
Organisme : NIGMS NIH HHS
ID : R01 GM124096
Pays : United States

Commentaires et corrections

Type : CommentIn

Informations de copyright

Copyright © 2023 Elsevier Inc. All rights reserved.

Déclaration de conflit d'intérêts

Declaration of interests The authors declare no competing interests.

Auteurs

Hongshan Zhang (H)

Center for Systems and Synthetic Biology, Institute for Cellular and Molecular Biology, Department of Molecular Biosciences, University of Texas at Austin, Austin, TX 78712, USA.

Zhubing Shi (Z)

Westlake Laboratory of Life Sciences and Biomedicine, Hangzhou 310024, Zhejiang, China; School of Life Sciences, Westlake University, Hangzhou 310024, Zhejiang, China; Department of Pharmacology, University of Texas Southwestern Medical Center, Dallas, TX 75390, USA.

Edward J Banigan (EJ)

Department of Physics, Institute for Medical Engineering and Science, Massachusetts Institute of Technology, Cambridge, MA 02139, USA.

Yoori Kim (Y)

Department of Pharmacology, University of Texas Southwestern Medical Center, Dallas, TX 75390, USA; Department of New Biology, Daegu Gyeongbuk Institute of Science and Technology, Daegu 42988, Republic of Korea.

Hongtao Yu (H)

Westlake Laboratory of Life Sciences and Biomedicine, Hangzhou 310024, Zhejiang, China; School of Life Sciences, Westlake University, Hangzhou 310024, Zhejiang, China; Department of Pharmacology, University of Texas Southwestern Medical Center, Dallas, TX 75390, USA. Electronic address: yuhongtao@westlake.edu.cn.

Xiao-Chen Bai (XC)

Department of Biophysics, Department of Cell Biology, University of Texas Southwestern Medical Center, Dallas, TX 75390, USA. Electronic address: xiaochen.bai@utsouthwestern.edu.

Ilya J Finkelstein (IJ)

Center for Systems and Synthetic Biology, Institute for Cellular and Molecular Biology, Department of Molecular Biosciences, University of Texas at Austin, Austin, TX 78712, USA. Electronic address: ilya@finkelsteinlab.org.

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Classifications MeSH

questionsmedicales.fr › Acides aminés, peptides et protéines › Protéines › Facteurs de transcription › Protéines de répression › Facteur de liaison à la séquence CCCTC › CTCF and R-loops are boundaries of...
questionsmedicales.fr › Phénomènes génétiques › Structures génétiques › Conformation d'acide nucléique › Structures en boucle R › CTCF and R-loops are boundaries of...
questionsmedicales.fr › Phénomènes génétiques › Structures génétiques › Structures de chromosome › Chromatine › CTCF and R-loops are boundaries of...
questionsmedicales.fr › Acides aminés, peptides et protéines › Protéines › Protéines du cycle cellulaire › CTCF and R-loops are boundaries of...
questionsmedicales.fr › Acides nucléiques, nucléotides et nucléosides › Acides nucléiques › ADN › CTCF and R-loops are boundaries of...