Evidence map›Paper›PMID 42030943›Full record

ArticleMolecular cell2026

Cohesin cofactor dosage sets the rate of loop extrusion, rendering genome folding tunable yet vulnerable to genetic disruption.

Rini Shah, Maxime M C Tortora, Nessim Louafi, Hadi Rahmaninejad, Karissa L Hansen, Erika C Anderson, Kenya Bonitto, David Wen, Luca Giorgetti, Geoffrey Fudenberg and 1 more

Abstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Molecular cell, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 5 papers.

0numbers the graph read from it
0cells of the map it votes in
5citing papers in PubMed
–field-weighted citation impact
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

5 citing papers in PubMed.

  1. Article
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4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

11 authors.

Rini ShahCardiovascular Research Institute, University of California, San Francisco, San Francisco, CA, USA.
Maxime M C TortoraDepartment of Quantitative and Computational Biology, University of Southern California, Los Angeles, CA, USA.
Nessim LouafiFriedrich Miescher Institute for Biomedical Research, Basel, Switzerland.
Hadi RahmaninejadDepartment of Quantitative and Computational Biology, University of Southern California, Los Angeles, CA, USA.
Karissa L HansenCardiovascular Research Institute, University of California, San Francisco, San Francisco, CA, USA; Developmental and Stem Cell Biology Graduate Program, University of California, San Francisco, San Francisco, CA, USA.
Erika C AndersonCardiovascular Research Institute, University of California, San Francisco, San Francisco, CA, USA.
Kenya BonittoCardiovascular Research Institute, University of California, San Francisco, San Francisco, CA, USA; Tetrad Graduate Program, University of California, San Francisco, San Francisco, CA, USA.
David WenCardiovascular Research Institute, University of California, San Francisco, San Francisco, CA, USA; Developmental and Stem Cell Biology Graduate Program, University of California, San Francisco, San Francisco, CA, USA.
Luca GiorgettiFriedrich Miescher Institute for Biomedical Research, Basel, Switzerland.
Geoffrey FudenbergDepartment of Quantitative and Computational Biology, University of Southern California, Los Angeles, CA, USA. Electronic address: fudenber@usc.edu.
Elphège P NoraCardiovascular Research Institute, University of California, San Francisco, San Francisco, CA, USA; Department of Biochemistry and Biophysics, University of California, San Francisco, San Francisco, CA, USA; Chan-Zuckerberg Biohub, San Francisco, CA, USA. Electronic address: elphege.nora@ucsf.edu.

Funding

PREDOCTORAL TRAINING IN DEVELOPMENTAL BIOLOGYT32HD007470 · NICHD · UNIVERSITY OF CALIFORNIA, SAN FRANCISCO · PI Todd Nystul · 1994 to 2026
$7.7M
Genomes in 3D: from maps to mechanismsR35GM143116 · NIGMS · UNIVERSITY OF SOUTHERN CALIFORNIA · PI FUDENBERG, GEOFFREY · 2021 to 2025
$2.1M
Investigating the role of genome folding in transcriptional regulationR35GM142792 · NIGMS · UNIVERSITY OF CALIFORNIA, SAN FRANCISCO · PI NORA, ELPHEGE-PIERRE JULIEN · 2021 to 2025
$2.0M
Illumina NovaSeq 6000 Sequencing SystemS10OD028511 · OD · UNIVERSITY OF CALIFORNIA, SAN FRANCISCO · PI CHOW, ERIC D · 2020 to 2020
$583k
NICHD NIH HHS T32 HD007470NIGMS NIH HHS R35 GM142792NIGMS NIH HHS R35 GM143116NIH HHS S10 OD028511
6 · The paper itself

Abstract

Genome folding is not static but emerges from dynamic processes that control transcription, replication, recombination, and repair. DNA loop extrusion by cohesin is central to genome organization, yet it remains unclear how cells can tune extrusion kinetics to achieve precise and functional chromosome folding patterns. Here, we show that extrusion rate acts as a tunable biophysical parameter in cells, quantitatively dialed by the respective dosage of the cohesin cofactors NIPBL and PDS5. Modulation of extrusion rate can offset changes in cohesin lifetime to buffer steady-state chromosome structure and transcriptional states, even in the face of abnormal extrusion dynamics. These findings provide a long-sought mechanistic basis for the genetic interactions between cohesin cofactors and for the molecular origin of haploinsufficiency in cohesinopathies, such as Cornelia de Lange syndrome.

Indexed as

Cell Cycle ProteinsChromosomal Proteins, Non-HistoneCohesinsDe Lange SyndromeHumansKineticsCell Cycle ProteinsChromosomal Proteins, Non-HistoneCohesinsNIPBL protein, humanchromosome foldingcohesin loop extrusiongenomic compartmentalizationhi-CNIPBL/SCC2polymer simulations

Identifiers

PMID42030943
PMCPMC13557204

What OpenQuestion holds

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Registered trials

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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.