Evidence map›Paper›PMID 35999210›Full record

ArticleNature communications2022

KLF4 recruits SWI/SNF to increase chromatin accessibility and reprogram the endothelial enhancer landscape under laminar shear stress.

Jan-Renier Moonen, James Chappell, Minyi Shi, Tsutomu Shinohara, Dan Li, Maxwell R Mumbach, Fan Zhang, Ramesh V Nair, Joseph Nasser, Daniel H Mai and 7 more

Open access · goldAbstract read
In one paragraph

Article in Nature communications, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 61 papers.

0numbers the graph read from it
0cells of the map it votes in
61citing papers in PubMed
5.2field-weighted citation impact, top 3% 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

61 citing papers in PubMed, 65 citations in OpenAlex.

  1. Review
  2. Gene-Specific Endothelial Programs Drive AVM Pathogenesis inArteriosclerosis, thrombosis, and vascular biology · 2026
    Article
  3. Article
  4. Article
  5. Article
  6. Article
  7. Article
  8. Vascular Aging.Circulation · 2026
    Review
  9. Article
  10. Enhancer Dynamics for Gene Regulation in the Cardiovascular System.Arteriosclerosis, thrombosis, and vascular biology · 2026
    Review
  11. Endothelial BMP6 Drives Hemodynamic-Dependent VSMCs Calcification in Carotid Atherosclerosis.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026
    Article
  12. Review
  13. Article
  14. Review
  15. Review
  16. Review
  17. The LFR-SWI/SNF complex: A chromatin wrench safeguarding cellular quiescence in theProceedings of the National Academy of Sciences of the United States of America · 2025
    Article
  18. Review
  19. Review
  20. Review

1 more citing papers are in PubMed but not listed here.

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

17 authors at 4 institutions in 1 country.

Jan-Renier Moonen *Vera Moulton Wall Center for Pulmonary Vascular Diseases, Stanford University School of Medicine, Stanford, CA, 94305, USA.ORCID 0000-0002-0361-824X
James Chappell *Department of Genetics, Stanford University School of Medicine, Stanford, CA, 94305, USA.
Minyi ShiDepartment of Genetics, Stanford University School of Medicine, Stanford, CA, 94305, USA.
Tsutomu ShinoharaVera Moulton Wall Center for Pulmonary Vascular Diseases, Stanford University School of Medicine, Stanford, CA, 94305, USA.
Dan LiVera Moulton Wall Center for Pulmonary Vascular Diseases, Stanford University School of Medicine, Stanford, CA, 94305, USA.
Maxwell R MumbachDepartment of Genetics, Stanford University School of Medicine, Stanford, CA, 94305, USA.
Fan ZhangVera Moulton Wall Center for Pulmonary Vascular Diseases, Stanford University School of Medicine, Stanford, CA, 94305, USA.ORCID 0000-0001-6884-9375
Ramesh V NairStanford Center for Genomics and Personalized Medicine, Stanford University School of Medicine, Stanford, CA, 94305, USA.
Joseph NasserBroad Institute of MIT and Harvard, Cambridge, MA, 02142, USA.
Daniel H MaiDepartment of Pediatrics, Stanford University School of Medicine, Stanford, CA, 94305, USA.ORCID 0000-0001-7661-6010
Shalina TaylorVera Moulton Wall Center for Pulmonary Vascular Diseases, Stanford University School of Medicine, Stanford, CA, 94305, USA.
Lingli WangVera Moulton Wall Center for Pulmonary Vascular Diseases, Stanford University School of Medicine, Stanford, CA, 94305, USA.
Ross J MetzgerVera Moulton Wall Center for Pulmonary Vascular Diseases, Stanford University School of Medicine, Stanford, CA, 94305, USA.ORCID 0000-0003-0069-4949
Howard Y ChangDepartment of Genetics, Stanford University School of Medicine, Stanford, CA, 94305, USA.ORCID 0000-0002-9459-4393
Jesse M EngreitzBASE Initiative, Betty Irene Moore Children's Heart Center, Lucile Packard Children's Hospital, Stanford University School of Medicine, Stanford, CA, 94305, USA.ORCID 0000-0002-5754-1719
Michael P SnyderStanford Cardiovascular Institute, Stanford University School of Medicine, Stanford, CA, 94305, USA.ORCID 0000-0003-0784-7987
Marlene RabinovitchVera Moulton Wall Center for Pulmonary Vascular Diseases, Stanford University School of Medicine, Stanford, CA, 94305, USA. marlener@stanford.edu.ORCID 0000-0001-7886-7104
Stanford University · USLucile Packard Children's Hospital · USCardiovascular Institute of the South · USBroad Institute · US

Funding

MICHIGAN INSTITUTE FOR CLINICAL AND HEALTH RESEARCH (MICHR) (UL1): (BPCA)UL1RR024986 · NCRR · UNIVERSITY OF MICHIGAN AT ANN ARBOR · PI SHANLEY, THOMAS P. · 2007 to 2011
$51.2M
WU P&FP30DK020579 · NIDDK · WASHINGTON UNIVERSITY · PI James Alexander Fitzpatrick · 2013 to 2026
$27.1M
Stanford Islet Research CoreP30DK116074 · NIDDK · STANFORD UNIVERSITY · PI Seung K Kim · 2017 to 2026
$19.5M
Pulmonary Hypertension in Genetically Modified MiceR01HL074186 · NHLBI · STANFORD UNIVERSITY · PI RABINOVITCH, MARLENE · 2004 to 2022
$10.4M
Pulmonary Hypertension Breakthrough InitiativeR24HL123767 · NHLBI · UNIVERSITY OF COLORADO DENVER · PI ALDRED, MICHEALA A, ERZURUM, SERPIL C. · 2014 to 2017
$10.1M
The BMP-PPARy Axis and Pulmonary HypertensionR01HL087118 · NHLBI · STANFORD UNIVERSITY · PI RABINOVITCH, MARLENE · 2008 to 2022
$7.2M
Integrative Omics as a Discovery Tool for Pulmonary HypertensionR01HL122887 · NHLBI · STANFORD UNIVERSITY · PI NICOLLS, MARK ROBERT, RABINOVITCH, MARLENE · 2015 to 2018
$4.1M
High Shear Stress Alters Gene Regulation in Pulmonary Arterial HypertensionR01HL152134 · NHLBI · STANFORD UNIVERSITY · PI RABINOVITCH, MARLENE · 2021 to 2024
$2.9M
Mapping enhancer-gene regulation in single cells to connect genetic variants to target genes and cell typesR35HG011324 · NHGRI · STANFORD UNIVERSITY · PI ENGREITZ, JESSE M · 2020 to 2024
$2.3M
Stanford Career Development Program in Omics of Lung DiseasesK12HL120001 · NHLBI · STANFORD UNIVERSITY · PI NICOLLS, MARK ROBERT, RABINOVITCH, MARLENE · 2013 to 2017
$1.3M
Systematic mapping and prediction of gene-enhancer connectionsR00HG009917 · NHGRI · STANFORD UNIVERSITY · PI ENGREITZ, JESSE M · 2020 to 2022
$796k
Ultra high throughput sequencer for sustaining and enhancing multi-scale genomic studiesS10OD025212 · OD · STANFORD UNIVERSITY · PI SNYDER, MICHAEL P. · 2018 to 2018
$600k
NCRR NIH HHS S10 RR027425NCRR NIH HHS UL1 RR024986NHGRI NIH HHS K99 HG009917NHGRI NIH HHS R00 HG009917NHGRI NIH HHS R35 HG011324NHLBI NIH HHS K12 HL120001NHLBI NIH HHS R01 HL074186NHLBI NIH HHS R01 HL087118NHLBI NIH HHS R01 HL122887NHLBI NIH HHS R01 HL152134NHLBI NIH HHS R24 HL123767NIDDK NIH HHS P30 DK020579NIDDK NIH HHS P30 DK116074NIH HHS S10 OD025212
6 · The paper itself

Abstract

Physiologic laminar shear stress (LSS) induces an endothelial gene expression profile that is vasculo-protective. In this report, we delineate how LSS mediates changes in the epigenetic landscape to promote this beneficial response. We show that under LSS, KLF4 interacts with the SWI/SNF nucleosome remodeling complex to increase accessibility at enhancer sites that promote the expression of homeostatic endothelial genes. By combining molecular and computational approaches we discover enhancers that loop to promoters of KLF4- and LSS-responsive genes that stabilize endothelial cells and suppress inflammation, such as BMPR2, SMAD5, and DUSP5. By linking enhancers to genes that they regulate under physiologic LSS, our work establishes a foundation for interpreting how non-coding DNA variants in these regions might disrupt protective gene expression to influence vascular disease.

Indexed as

ChromatinEndothelial CellsChromatin Assembly and DisassemblyNucleosomesRegulatory Sequences, Nucleic AcidChromatinNucleosomes

Identifiers

PMID35999210
PMCPMC9399231
OpenAlexW4292696641

What OpenQuestion holds

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LicenceCC BY
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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.