IDEAS home Printed from https://ideas.repec.org/a/nat/natcom/v13y2022i1d10.1038_s41467-022-32566-9.html
   My bibliography  Save this article

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

Author

Listed:
  • Jan-Renier Moonen

    (Stanford University School of Medicine
    Stanford University School of Medicine
    Stanford University School of Medicine
    Stanford University School of Medicine)

  • James Chappell

    (Stanford University School of Medicine)

  • Minyi Shi

    (Stanford University School of Medicine)

  • Tsutomu Shinohara

    (Stanford University School of Medicine
    Stanford University School of Medicine
    Stanford University School of Medicine
    Stanford University School of Medicine)

  • Dan Li

    (Stanford University School of Medicine
    Stanford University School of Medicine
    Stanford University School of Medicine)

  • Maxwell R. Mumbach

    (Stanford University School of Medicine
    Stanford University School of Medicine)

  • Fan Zhang

    (Stanford University School of Medicine
    Stanford University School of Medicine)

  • Ramesh V. Nair

    (Stanford University School of Medicine)

  • Joseph Nasser

    (Broad Institute of MIT and Harvard)

  • Daniel H. Mai

    (Stanford University School of Medicine)

  • Shalina Taylor

    (Stanford University School of Medicine
    Stanford University School of Medicine
    Stanford University School of Medicine)

  • Lingli Wang

    (Stanford University School of Medicine
    Stanford University School of Medicine
    Stanford University School of Medicine
    Stanford University School of Medicine)

  • Ross J. Metzger

    (Stanford University School of Medicine
    Stanford University School of Medicine)

  • Howard Y. Chang

    (Stanford University School of Medicine
    Stanford University School of Medicine)

  • Jesse M. Engreitz

    (Stanford University School of Medicine
    Stanford University School of Medicine
    Broad Institute of MIT and Harvard)

  • Michael P. Snyder

    (Stanford University School of Medicine
    Stanford University School of Medicine
    Stanford University School of Medicine)

  • Marlene Rabinovitch

    (Stanford University School of Medicine
    Stanford University School of Medicine
    Stanford University School of Medicine
    Stanford University School of Medicine)

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.

Suggested Citation

  • Jan-Renier Moonen & James Chappell & Minyi Shi & Tsutomu Shinohara & Dan Li & Maxwell R. Mumbach & Fan Zhang & Ramesh V. Nair & Joseph Nasser & Daniel H. Mai & Shalina Taylor & Lingli Wang & Ross J. M, 2022. "KLF4 recruits SWI/SNF to increase chromatin accessibility and reprogram the endothelial enhancer landscape under laminar shear stress," Nature Communications, Nature, vol. 13(1), pages 1-16, December.
    • Handle: RePEc:nat:natcom:v:13:y:2022:i:1:d:10.1038_s41467-022-32566-9
    DOI: 10.1038/s41467-022-32566-9
    as

    Download full text from publisher

    File URL: https://www.nature.com/articles/s41467-022-32566-9
    File Function: Abstract
    Download Restriction: no
    File URL: https://libkey.io/10.1038/s41467-022-32566-9?utm_source=ideas
    LibKey link: if access is restricted and if your library uses this service, LibKey will redirect you to where you can use your library subscription to access this item
    ---><---

    References listed on IDEAS

    as
    1. Eleni Tzima & Mohamed Irani-Tehrani & William B. Kiosses & Elizabetta Dejana & David A. Schultz & Britta Engelhardt & Gaoyuan Cao & Horace DeLisser & Martin Alexander Schwartz, 2005. "A mechanosensory complex that mediates the endothelial cell response to fluid shear stress," Nature, Nature, vol. 437(7057), pages 426-431, September.
    2. Armando Reyes-Palomares & Mingxia Gu & Fabian Grubert & Ivan Berest & Silin Sa & Maya Kasowski & Christian Arnold & Mao Shuai & Rohith Srivas & Simon Miao & Dan Li & Michael P. Snyder & Marlene Rabino, 2020. "Remodeling of active endothelial enhancers is associated with aberrant gene-regulatory networks in pulmonary arterial hypertension," Nature Communications, Nature, vol. 11(1), pages 1-14, December.
    3. Jennifer S. Fang & Brian G. Coon & Noelle Gillis & Zehua Chen & Jingyao Qiu & Thomas W. Chittenden & Janis M. Burt & Martin A. Schwartz & Karen K. Hirschi, 2017. "Shear-induced Notch-Cx37-p27 axis arrests endothelial cell cycle to enable arterial specification," Nature Communications, Nature, vol. 8(1), pages 1-14, December.
    4. Marco Osterwalder & Iros Barozzi & Virginie Tissières & Yoko Fukuda-Yuzawa & Brandon J. Mannion & Sarah Y. Afzal & Elizabeth A. Lee & Yiwen Zhu & Ingrid Plajzer-Frick & Catherine S. Pickle & Momoe Kat, 2018. "Enhancer redundancy provides phenotypic robustness in mammalian development," Nature, Nature, vol. 554(7691), pages 239-243, February.
    5. Burak H. Alver & Kimberly H. Kim & Ping Lu & Xiaofeng Wang & Haley E. Manchester & Weishan Wang & Jeffrey R. Haswell & Peter J. Park & Charles W. M. Roberts, 2017. "The SWI/SNF chromatin remodelling complex is required for maintenance of lineage specific enhancers," Nature Communications, Nature, vol. 8(1), pages 1-10, April.
    6. Yifei Miao & Nassim E. Ajami & Tse-Shun Huang & Feng-Mao Lin & Chih-Hong Lou & Yun-Ting Wang & Shuai Li & Jian Kang & Hannah Munkacsi & Mano R. Maurya & Shakti Gupta & Shu Chien & Shankar Subramaniam , 2018. "Enhancer-associated long non-coding RNA LEENE regulates endothelial nitric oxide synthase and endothelial function," Nature Communications, Nature, vol. 9(1), pages 1-13, December.
    Full references (including those not matched with items on IDEAS)

    Most related items

    These are the items that most often cite the same works as this one and are cited by the same works as this one.
    1. Andrea Wilderman & Eva D’haene & Machteld Baetens & Tara N. Yankee & Emma Wentworth Winchester & Nicole Glidden & Ellen Roets & Jo Dorpe & Sandra Janssens & Danny E. Miller & Miranda Galey & Kari M. B, 2024. "A distant global control region is essential for normal expression of anterior HOXA genes during mouse and human craniofacial development," Nature Communications, Nature, vol. 15(1), pages 1-23, December.
    2. Jin Woo Oh & Michael A. Beer, 2024. "Gapped-kmer sequence modeling robustly identifies regulatory vocabularies and distal enhancers conserved between evolutionarily distant mammals," Nature Communications, Nature, vol. 15(1), pages 1-16, December.
    3. Eun-A Kwak & Christopher C. Pan & Aaron Ramonett & Sanjay Kumar & Paola Cruz-Flores & Tasmia Ahmed & Hannah R. Ortiz & Jeffrey J. Lochhead & Nathan A. Ellis & Ghassan Mouneimne & Teodora G. Georgieva , 2022. "βIV-spectrin as a stalk cell-intrinsic regulator of VEGF signaling," Nature Communications, Nature, vol. 13(1), pages 1-14, December.
    4. Vincent Loubiere & Bernardo P. Almeida & Michaela Pagani & Alexander Stark, 2024. "Developmental and housekeeping transcriptional programs display distinct modes of enhancer-enhancer cooperativity in Drosophila," Nature Communications, Nature, vol. 15(1), pages 1-11, December.
    5. Jonas Stewen & Kai Kruse & Anca T. Godoi-Filip & Zenia & Hyun-Woo Jeong & Susanne Adams & Frank Berkenfeld & Martin Stehling & Kristy Red-Horse & Ralf H. Adams & Mara E. Pitulescu, 2024. "Eph-ephrin signaling couples endothelial cell sorting and arterial specification," Nature Communications, Nature, vol. 15(1), pages 1-23, December.
    6. Samuel Abassah-Oppong & Matteo Zoia & Brandon J. Mannion & Raquel Rouco & Virginie Tissières & Cailyn H. Spurrell & Virginia Roland & Fabrice Darbellay & Anja Itum & Julie Gamart & Tabitha A. Festa-Da, 2024. "A gene desert required for regulatory control of pleiotropic Shox2 expression and embryonic survival," Nature Communications, Nature, vol. 15(1), pages 1-24, December.
    7. Raquel Rouco & Olimpia Bompadre & Antonella Rauseo & Olivier Fazio & Rodrigue Peraldi & Fabrizio Thorel & Guillaume Andrey, 2021. "Cell-specific alterations in Pitx1 regulatory landscape activation caused by the loss of a single enhancer," Nature Communications, Nature, vol. 12(1), pages 1-15, December.
    8. Matthew J Harder & Julie Hix & Wendy M Reeves & Michael T Veeman, 2021. "Ciona Brachyury proximal and distal enhancers have different FGF dose-response relationships," PLOS Genetics, Public Library of Science, vol. 17(1), pages 1-23, January.
    9. Daniela Michelatti & Sven Beyes & Chiara Bernardis & Maria Luce Negri & Leonardo Morelli & Naiara Garcia Bediaga & Vittoria Poli & Luca Fagnocchi & Sara Lago & Sarah D’Annunzio & Nicole Cona & Ilaria , 2024. "Oncogenic enhancers prime quiescent metastatic cells to escape NK immune surveillance by eliciting transcriptional memory," Nature Communications, Nature, vol. 15(1), pages 1-24, December.
    10. Christopher Chase Bolt & Lucille Lopez-Delisle & Aurélie Hintermann & Bénédicte Mascrez & Antonella Rauseo & Guillaume Andrey & Denis Duboule, 2022. "Context-dependent enhancer function revealed by targeted inter-TAD relocation," Nature Communications, Nature, vol. 13(1), pages 1-15, December.
    11. Fabrice Darbellay & Anna Ramisch & Lucille Lopez-Delisle & Michael Kosicki & Antonella Rauseo & Zahra Jouini & Axel Visel & Guillaume Andrey, 2024. "Pre-hypertrophic chondrogenic enhancer landscape of limb and axial skeleton development," Nature Communications, Nature, vol. 15(1), pages 1-15, December.
    12. Matthieu Santos & Stéphanie Backer & Frédéric Auradé & Matthew Man-Kin Wong & Maud Wurmser & Rémi Pierre & Francina Langa & Marcio Cruzeiro & Alain Schmitt & Jean-Paul Concordet & Athanassia Sotiropou, 2022. "A fast Myosin super enhancer dictates muscle fiber phenotype through competitive interactions with Myosin genes," Nature Communications, Nature, vol. 13(1), pages 1-17, December.
    13. Gang Ren & Wai Lim Ku & Guangzhe Ge & Jackson A. Hoffman & Jee Youn Kang & Qingsong Tang & Kairong Cui & Yong He & Yukun Guan & Bin Gao & Chengyu Liu & Trevor K. Archer & Keji Zhao, 2024. "Acute depletion of BRG1 reveals its primary function as an activator of transcription," Nature Communications, Nature, vol. 15(1), pages 1-16, December.
    14. Xuemeng Zhou & Tsz Wing Sam & Ah Young Lee & Danny Leung, 2021. "Mouse strain-specific polymorphic provirus functions as cis-regulatory element leading to epigenomic and transcriptomic variations," Nature Communications, Nature, vol. 12(1), pages 1-18, December.
    15. Riccardo Calandrelli & Xingzhao Wen & John Lalith Charles Richard & Zhifei Luo & Tri C. Nguyen & Chien-Ju Chen & Zhijie Qi & Shuanghong Xue & Weizhong Chen & Zhangming Yan & Weixin Wu & Kathia Zaleta-, 2023. "Genome-wide analysis of the interplay between chromatin-associated RNA and 3D genome organization in human cells," Nature Communications, Nature, vol. 14(1), pages 1-14, December.
    16. Susanne Fleig & Tamar Kapanadze & Jeremiah Bernier-Latmani & Julia K. Lill & Tania Wyss & Jaba Gamrekelashvili & Dustin Kijas & Bin Liu & Anne M. Hüsing & Esther Bovay & Adan Chari Jirmo & Stephan Hal, 2022. "Loss of vascular endothelial notch signaling promotes spontaneous formation of tertiary lymphoid structures," Nature Communications, Nature, vol. 13(1), pages 1-14, December.
    17. Arthur S. Lee & Lauren J. Ayers & Michael Kosicki & Wai-Man Chan & Lydia N. Fozo & Brandon M. Pratt & Thomas E. Collins & Boxun Zhao & Matthew F. Rose & Alba Sanchis-Juan & Jack M. Fu & Isaac Wong & X, 2024. "A cell type-aware framework for nominating non-coding variants in Mendelian regulatory disorders," Nature Communications, Nature, vol. 15(1), pages 1-26, December.
    18. Sandra Kessler & Maryline Minoux & Onkar Joshi & Yousra Zouari & Sebastien Ducret & Fiona Ross & Nathalie Vilain & Adwait Salvi & Joachim Wolff & Hubertus Kohler & Michael B. Stadler & Filippo M. Rijl, 2023. "A multiple super-enhancer region establishes inter-TAD interactions and controls Hoxa function in cranial neural crest," Nature Communications, Nature, vol. 14(1), pages 1-22, December.
    19. Markus Götz & Olivier Messina & Sergio Espinola & Jean-Bernard Fiche & Marcelo Nollmann, 2022. "Multiple parameters shape the 3D chromatin structure of single nuclei at the doc locus in Drosophila," Nature Communications, Nature, vol. 13(1), pages 1-14, December.
    20. Cheng Zeng & Jiwei Chen & Emmalee W. Cooke & Arijita Subuddhi & Eliana T. Roodman & Fei Xavier Chen & Kaixiang Cao, 2023. "Demethylase-independent roles of LSD1 in regulating enhancers and cell fate transition," Nature Communications, Nature, vol. 14(1), pages 1-15, December.

    More about this item

    Statistics

    Access and download statistics

    Corrections

    All material on this site has been provided by the respective publishers and authors. You can help correct errors and omissions. When requesting a correction, please mention this item's handle: RePEc:nat:natcom:v:13:y:2022:i:1:d:10.1038_s41467-022-32566-9. See general information about how to correct material in RePEc.

    If you have authored this item and are not yet registered with RePEc, we encourage you to do it here. This allows to link your profile to this item. It also allows you to accept potential citations to this item that we are uncertain about.

    If CitEc recognized a bibliographic reference but did not link an item in RePEc to it, you can help with this form .

    If you know of missing items citing this one, you can help us creating those links by adding the relevant references in the same way as above, for each refering item. If you are a registered author of this item, you may also want to check the "citations" tab in your RePEc Author Service profile, as there may be some citations waiting for confirmation.

    For technical questions regarding this item, or to correct its authors, title, abstract, bibliographic or download information, contact: Sonal Shukla or Springer Nature Abstracting and Indexing (email available below). General contact details of provider: http://www.nature.com .

    Please note that corrections may take a couple of weeks to filter through the various RePEc services.

    IDEAS is a RePEc service. RePEc uses bibliographic data supplied by the respective publishers.