Two CTCF motifs impede cohesin-mediated DNA loop extrusion

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Two CTCF motifs impede cohesin-mediated DNA loop extrusion

Journal Article (2025)

Author(s)

Roman Barth (Kavli institute of nanoscience Delft, BN/Cees Dekker Lab)

Richard Janissen (Kavli institute of nanoscience Delft, TU Delft - BN/Bionanoscience)

Laura Muras (BN/Cees Dekker Lab, Kavli institute of nanoscience Delft, TU Delft - BN/Bionanoscience)

Jaco van der Torre (BN/Cees Dekker Lab, Kavli institute of nanoscience Delft)

Gabriele Litos (Research Institute of Molecular Pathology, Vienna)

Eli van der Sluis (TU Delft - BN/Marileen Dogterom Lab, Kavli institute of nanoscience Delft)

Ashmiani van den Berg (Kavli institute of nanoscience Delft, BN/Cees Dekker Lab)

Iain F. Davidson (Research Institute of Molecular Pathology, Vienna)

Jan Michael Peters (Research Institute of Molecular Pathology, Vienna)

Cees Dekker (BN/Cees Dekker Lab, Kavli institute of nanoscience Delft)

BN/Cees Dekker Lab

DOI related publication

https://doi.org/10.1016/j.molcel.2025.11.001

Magnetic tweezers Chromosome organization Cohesin Single-molecule fluorescence DNA loop extrusion CTCF AlphaFold

To reference this document use:

https://resolver.tudelft.nl/uuid:5704f3d4-b56f-44b4-b404-806c3ae70f51

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Publication Year

2025

Language

English

BN/Cees Dekker Lab

Bibliographical Note

Green Open Access added to TU Delft Institutional Repository 'You share, we take care!' - Taverne project https://www.openaccess.nl/en/publishing/publisher-deals Otherwise as indicated in the copyright section: the publisher is the copyright holder of this work and the author uses the Dutch legislation to make this work public.

Journal title

Molecular cell

Issue number

23

Volume number

85

Pages (from-to)

4304-4317.e9

Downloads counter

85

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Abstract

Human cohesin extrudes DNA into loops and is positioned along the genome by stalling at the human CCCTC-binding factor (CTCF) upon encountering its N-terminal region (NTR). The mechanism underlying this stalling, however, is unresolved. Using single-molecule assays that monitor DNA loop extrusion (LE) in the presence of NTR fragments, we identify two amino acid motifs, YDF and KTYQR, which hinder LE. KTYQR is found to completely block LE activity, while YDF hinders cohesin from completing LE step cycles and converts cohesin into a unidirectional extruder by strengthening the affinity of STAG1 to DNA. We thus identify two distinct NTR motifs that stall LE via different yet synergistic mechanisms, highlighting the multifaceted ways employed by CTCF to modulate LE to shape and regulate genomes.

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