Show simple item record

dc.contributor.authorLe, Huy Q
dc.contributor.authorHill, Matthew
dc.contributor.authorKollak, Ines
dc.contributor.authorKeck, Martina
dc.contributor.authorSchroeder, Victoria
dc.contributor.authorWirth, Johannes
dc.contributor.authorSkronska-Wasek, Wioletta
dc.contributor.authorSchruf, Eva
dc.contributor.authorStrobel, Benjamin
dc.contributor.authorStahl, Heiko
dc.contributor.authorHerrmann, Franziska E
dc.contributor.authorCampos, Alexandre R
dc.contributor.authorLi, Jun
dc.contributor.authorQuast, Karsten
dc.contributor.authorKnebel, Dagmar
dc.contributor.authorViollet, Coralie
dc.contributor.authorThomas, Matthew J
dc.contributor.authorLamb, David
dc.contributor.authorGarnett, James P
dc.date.accessioned2021-12-08T00:30:21Z
dc.date.available2021-12-08T00:30:21Z
dc.date.issued2021-08-04
dc.identifier.issn1469-221X
dc.identifier.urihttps://www.repository.cam.ac.uk/handle/1810/331261
dc.description.abstractUnveiling the molecular mechanisms of tissue remodelling following injury is imperative to elucidate its regenerative capacity and aberrant repair in disease. Using different omics approaches, we identified enhancer of zester homolog 2 (EZH2) as a key regulator of fibrosis in injured lung epithelium. Epithelial injury drives an enrichment of nuclear transforming growth factor-β-activated kinase 1 (TAK1) that mediates EZH2 phosphorylation to facilitate its liberation from polycomb repressive complex 2 (PRC2). This process results in the establishment of a transcriptional complex of EZH2, RNA-polymerase II (POL2) and nuclear actin, which orchestrates aberrant epithelial repair programmes. The liberation of EZH2 from PRC2 is accompanied by an EZH2-EZH1 switch to preserve H3K27me3 deposition at non-target genes. Loss of epithelial TAK1, EZH2 or blocking nuclear actin influx attenuates the fibrotic cascade and restores respiratory homeostasis. Accordingly, EZH2 inhibition significantly improves outcomes in a pulmonary fibrosis mouse model. Our results reveal an important non-canonical function of EZH2, paving the way for new therapeutic interventions in fibrotic lung diseases.
dc.publisherWiley
dc.rightsAttribution-NonCommercial-NoDerivatives 4.0 International
dc.rights.urihttps://creativecommons.org/licenses/by-nc-nd/4.0/
dc.titleAn EZH2-dependent transcriptional complex promotes aberrant epithelial remodelling after injury.
dc.typeArticle
dc.publisher.departmentWellcome Trust/Cancer Research Uk Gurdon Institute
dc.date.updated2021-12-06T10:06:33Z
prism.issueIdentifier8
prism.publicationDate2021
prism.publicationNameEMBO Reports
prism.startingPagee52785
prism.volume22
dc.identifier.doi10.17863/CAM.78707
dcterms.dateAccepted2021-06-10
rioxxterms.versionofrecord10.15252/embr.202152785
rioxxterms.versionVoR
dc.contributor.orcidLe, Huy Q [0000-0002-0851-9320]
dc.contributor.orcidStrobel, Benjamin [0000-0002-8687-3499]
dc.identifier.eissn1469-3178
rioxxterms.typeJournal Article/Review
cam.issuedOnline2021-07-05
cam.depositDate2021-12-06
pubs.licence-identifierapollo-deposit-licence-2-1
pubs.licence-display-nameApollo Repository Deposit Licence Agreement


Files in this item

Thumbnail

This item appears in the following Collection(s)

Show simple item record

Attribution-NonCommercial-NoDerivatives 4.0 International
Except where otherwise noted, this item's licence is described as Attribution-NonCommercial-NoDerivatives 4.0 International