Evidence map›Paper›PMID 42127908›Full record

ArticleMolecular cell2026

Transcription and cohesin direct domain boundary spatial positioning and are linked to Friedreich's ataxia.

Ashley Karnay, Ricardo Linares-Saldana, Qiaohong Wang, Zachary Gardner, Jialiu A Liang, Garrett T Santini, Krishna Kumar Haridhasapavalan, Son C Nguyen, Siewert Hugelier, Bhavana Shewale and 11 more

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Article in Molecular cell, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.

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1 · What the graph read from it

What it found

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2 · The registry

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3 · Its place in the literature

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4 · The record

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5 · Who and what money

Authors and funding

21 authors.

Ashley KarnayDepartment of Cell and Developmental Biology, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA 19104, USA; Epigenetics Institute, Pereleman School of Medicine, University of Pennsylvania, Philadelphia, PA 19104, USA.
Ricardo Linares-SaldanaDepartment of Cell and Developmental Biology, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA 19104, USA; Epigenetics Institute, Pereleman School of Medicine, University of Pennsylvania, Philadelphia, PA 19104, USA.
Qiaohong WangDepartment of Cell and Developmental Biology, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA 19104, USA; Epigenetics Institute, Pereleman School of Medicine, University of Pennsylvania, Philadelphia, PA 19104, USA.
Zachary GardnerDepartment of Cell and Developmental Biology, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA 19104, USA; Epigenetics Institute, Pereleman School of Medicine, University of Pennsylvania, Philadelphia, PA 19104, USA.
Jialiu A LiangDepartment of Cell and Developmental Biology, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA 19104, USA; Epigenetics Institute, Pereleman School of Medicine, University of Pennsylvania, Philadelphia, PA 19104, USA.
Garrett T SantiniDepartment of Cell and Developmental Biology, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA 19104, USA; Epigenetics Institute, Pereleman School of Medicine, University of Pennsylvania, Philadelphia, PA 19104, USA.
Krishna Kumar HaridhasapavalanDepartment of Cell and Developmental Biology, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA 19104, USA; Epigenetics Institute, Pereleman School of Medicine, University of Pennsylvania, Philadelphia, PA 19104, USA.
Son C NguyenEpigenetics Institute, Pereleman School of Medicine, University of Pennsylvania, Philadelphia, PA 19104, USA; Department of Genetics, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA 19104, USA.
Siewert HugelierDepartment of Physiology, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA 19104, USA.
Bhavana ShewaleDepartment of Cell, Developmental and Regenerative Biology, Icahn School of Medicine at Mount Sinai, New York, NY 10029, USA.
Masato T KanemakiDepartment of Biological Sciences, Graduate School of Science, National Institute of Genetics, Research Organization of Information and Systems (ROIS), Mishima, Shizuoka 411-8540, Japan; Graduate Institute for Advanced Studies, SOKENDAI, Mishima, Shizuoka 411-8540, Japan; Department of Biological Science, The University of Tokyo, Bunkyo-ku, Tokyo 113-0033, Japan.
Jill S NapieralaDepartment of Neurology, Peter O'Donnell Jr. Brain Institute, University of Texas Southwestern Medical Center, Dallas, TX 75390, USA.
Marek NapieralaDepartment of Neurology, Peter O'Donnell Jr. Brain Institute, University of Texas Southwestern Medical Center, Dallas, TX 75390, USA.
Robert B WilsonDepartment of Pathology and Laboratory Medicine, Penn/CHOP Center of Excellence for Friedreich's Ataxia Research, Children's Hospital of Philadelphia, Philadelphia, PA 19104, USA.
Nicole DuboisDepartment of Cell, Developmental and Regenerative Biology, Icahn School of Medicine at Mount Sinai, New York, NY 10029, USA.
Andrey PoleshkoDepartment of Cell and Developmental Biology, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA 19104, USA; Epigenetics Institute, Pereleman School of Medicine, University of Pennsylvania, Philadelphia, PA 19104, USA.
Wonho KimDepartment of Cell and Developmental Biology, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA 19104, USA; Epigenetics Institute, Pereleman School of Medicine, University of Pennsylvania, Philadelphia, PA 19104, USA; Department of Genetics, Integrative Program for Biological and Genome Sciences, University of North Carolina, Chapel Hill, NC 27599, USA.
Parisha P ShahDepartment of Cell and Developmental Biology, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA 19104, USA; Epigenetics Institute, Pereleman School of Medicine, University of Pennsylvania, Philadelphia, PA 19104, USA.
Melike LakadamyaliEpigenetics Institute, Pereleman School of Medicine, University of Pennsylvania, Philadelphia, PA 19104, USA; Department of Physiology, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA 19104, USA.
Eric F JoyceEpigenetics Institute, Pereleman School of Medicine, University of Pennsylvania, Philadelphia, PA 19104, USA; Department of Genetics, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA 19104, USA.
Rajan JainDepartment of Cell and Developmental Biology, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA 19104, USA; Epigenetics Institute, Pereleman School of Medicine, University of Pennsylvania, Philadelphia, PA 19104, USA; Department of Medicine, Penn Cardiovascular Institute, Institute of Regenerative Medicine, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA 19104, USA. Electronic address: jainr@pennmedicine.upenn.edu.

Funding

Training Program in Cardiovascular Biology and MedicineT32HL007843 · NHLBI · UNIVERSITY OF PENNSYLVANIA · PI THOMAS P. CAPPOLA, Sharlene M Day · 1996 to 2026
$11.0M
PREDOCTORAL TRAINING PROGRAM IN GENETICST32GM008216 · NIGMS · UNIVERSITY OF PENNSYLVANIA · PI EPSTEIN, DOUGLAS J · 1987 to 2023
$8.3M
Graduate Training in Developmental BiologyT32HD083185 · NICHD · UNIVERSITY OF PENNSYLVANIA · PI Michael Granato, Foteini Mourkioti · 2015 to 2026
$4.0M
Deciphering how 3D genome organization orchestrates cardiac cellular identityR35HL166663 · NHLBI · UNIVERSITY OF PENNSYLVANIA · PI Rajan Jain · 2023 to 2026
$3.5M
Single-cell dissection of chromatin architecture mechanisms connecting pathologic instability and transcriptional silencingU01DA052715 · NIDA · UNIVERSITY OF PENNSYLVANIA · PI JAIN, RAJAN, JOYCE, ERIC F. · 2020 to 2024
$3.1M
Understanding the role of tether proteins to maintain chromatin-nuclear lamina contacts in premature aging.R21AG081795 · NIA · UNIVERSITY OF PENNSYLVANIA · PI POLESHKO, ANDREY · 2023 to 2024
$447k
NHLBI NIH HHS R35 HL166663NHLBI NIH HHS T32 HL007843NIA NIH HHS R21 AG081795NICHD NIH HHS T32 HD083185NIDA NIH HHS U01 DA052715NIGMS NIH HHS T32 GM008216
6 · The paper itself

Abstract

Variability in genome organization drives differential gene expression and shapes cellular diversity, yet whether transcription actively instructs genome structure and how this relationship is exploited in disease remains unclear. We show that transcription and cohesin direct the spatial positioning of lamina-associated domain (LAD) boundary genes. Transcriptional repression repositions LAD boundary genes to the nuclear lamina in a cohesin loop extrusion-dependent manner. Conversely, overactive cohesin is sufficient to reposition and silence LAD boundary genes, an effect counteracted by maintaining transcription. In Friedreich's ataxia, we demonstrate improper positioning of the pathogenically repressed LAD boundary gene FRATAXIN (FXN) at the nuclear periphery reflects an imbalance between transcription and cohesin dynamics. Importantly, modulating either transcription or cohesin activity restores FXN positioning and reactivates expression. Our findings establish transcription and cohesin as tunable molecular rheostats orchestrating LAD boundary spatial positioning and reveal how the flexible and dynamic nature of genome architecture is hijacked in disease.

Indexed as

CohesinsFrataxinFriedreich AtaxiaGene Expression RegulationGenome, HumanNuclear LaminaTranscription, GeneticCell Cycle ProteinsChondroitin Sulfate ProteoglycansChromosomal Proteins, Non-HistoneDNA-Binding ProteinsFibroblastsGene SilencingHEK293 CellsHumansCell Cycle ProteinsChondroitin Sulfate ProteoglycansChromosomal Proteins, Non-HistoneCohesinsDNA-Binding ProteinsFrataxinFXN protein, humanNIPBL protein, humanRAD21 protein, humanSMC3 protein, human3D spatial positioningcohesiondiseaseFriedreich’s ataxiaFXNgenome organizationhiPSCLADsplasticitytranscription

Identifiers

PMID42127908
PMCPMC13274809

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