Evidence map›Paper›PMID 36449519›Full record

ArticlePLoS genetics2022

Co-depletion of NIPBL and WAPL balance cohesin activity to correct gene misexpression.

Jennifer M Luppino, Andrew Field, Son C Nguyen, Daniel S Park, Parisha P Shah, Richard J Abdill, Yemin Lan, Rebecca Yunker, Rajan Jain, Karen Adelman and 1 more

Open access · goldAbstract read
In one paragraph

Article in PLoS genetics, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 21 papers.

0numbers the graph read from it
0cells of the map it votes in
21citing papers in PubMed
1.5field-weighted citation impact, top 18% of its field
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

21 citing papers in PubMed, 22 citations in OpenAlex.

  1. Review
  2. Article
  3. Re-establishment of TAD boundary organization during DNA replication.bioRxiv : the preprint server for biology · 2026
    Article
  4. Article
  5. Article
  6. Article
  7. Article
  8. Article
  9. Clinical,medRxiv : the preprint server for health sciences · 2026
    Article
  10. TAD boundaries and gene activity are uncoupled.bioRxiv : the preprint server for biology · 2026
    Article
  11. Article
  12. Article
  13. Review
  14. Article
  15. Article
  16. Article
  17. Article
  18. Article
  19. Cohesin regulation and roles in chromosome structure and function.Current opinion in genetics & development · 2024
    Review
  20. Article
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 at 3 institutions in 1 country.

Jennifer M LuppinoDepartment of Genetics, Perelman School of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania, United States of America.ORCID 0000-0002-2078-7619
Andrew FieldDepartment of Biological Chemistry and Molecular Pharmacology, Blavatnik Institute, Harvard Medical School, Boston, Massachusetts, United States of America.
Son C NguyenDepartment of Genetics, Perelman School of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania, United States of America.
Daniel S ParkDepartment of Genetics, Perelman School of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania, United States of America.
Parisha P ShahPenn Epigenetics Institute, University of Pennsylvania, Philadelphia, Pennsylvania, United States of America.
Richard J AbdillDepartment of Genetics, Perelman School of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania, United States of America.ORCID 0000-0001-9565-5832
Yemin LanPenn Epigenetics Institute, University of Pennsylvania, Philadelphia, Pennsylvania, United States of America.
Rebecca YunkerDepartment of Genetics, Perelman School of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania, United States of America.
Rajan JainPenn Epigenetics Institute, University of Pennsylvania, Philadelphia, Pennsylvania, United States of America.
Karen AdelmanDepartment of Biological Chemistry and Molecular Pharmacology, Blavatnik Institute, Harvard Medical School, Boston, Massachusetts, United States of America.
Eric F JoyceDepartment of Genetics, Perelman School of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania, United States of America.ORCID 0000-0002-0418-2804
University of Pennsylvania · USBroad Institute · USHarvard University · US

Funding

Regulation of chromatin folding in space and timeR35GM128903 · NIGMS · UNIVERSITY OF PENNSYLVANIA · PI Eric F. Joyce · 2018 to 2026
$4.2M
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
The Role of BRD4 in Cardiac SpecificationR01HL139783 · NHLBI · UNIVERSITY OF PENNSYLVANIA · PI JAIN, RAJAN · 2019 to 2022
$1.6M
Evaluating novel architectural proteins as therapeutic targets for cohesin dysfunctionR21HD107261 · NICHD · UNIVERSITY OF PENNSYLVANIA · PI JOYCE, ERIC F. · 2022 to 2023
$447k
NHLBI NIH HHS R01 HL139783NICHD NIH HHS R21 HD107261NIDA NIH HHS U01 DA052715NIGMS NIH HHS R35 GM128903
6 · The paper itself

Abstract

The relationship between cohesin-mediated chromatin looping and gene expression remains unclear. NIPBL and WAPL are two opposing regulators of cohesin activity; depletion of either is associated with changes in both chromatin folding and transcription across a wide range of cell types. However, a direct comparison of their individual and combined effects on gene expression in the same cell type is lacking. We find that NIPBL or WAPL depletion in human HCT116 cells each alter the expression of ~2,000 genes, with only ~30% of the genes shared between the conditions. We find that clusters of differentially expressed genes within the same topologically associated domain (TAD) show coordinated misexpression, suggesting some genomic domains are especially sensitive to both more or less cohesin. Finally, co-depletion of NIPBL and WAPL restores the majority of gene misexpression as compared to either knockdown alone. A similar set of NIPBL-sensitive genes are rescued following CTCF co-depletion. Together, this indicates that altered transcription due to reduced cohesin activity can be functionally offset by removal of either its negative regulator (WAPL) or the physical barriers (CTCF) that restrict loop-extrusion events.

Indexed as

Cell Cycle ProteinsChromatinChromosomal Proteins, Non-HistoneGene Expression RegulationCarrier ProteinsCCCTC-Binding FactorCohesinsGenes, cdcGenomeHCT116 CellsHumansNuclear ProteinsProto-Oncogene ProteinsCarrier ProteinsCCCTC-Binding FactorCell Cycle ProteinsChromatinChromosomal Proteins, Non-HistoneCohesinsNIPBL protein, humanNuclear ProteinsProto-Oncogene ProteinsWAPL protein, human

Identifiers

PMID36449519
PMCPMC9744307
OpenAlexW4310433598

What Socratic holds

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LicenceCC BY
Read underepoch 390

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 Socratic graph.