PXD025677-1
PXD025677 is an original dataset announced via ProteomeXchange.
Dataset Summary
| Title | EZH2-dependent transcriptional complex promotes aberrant epithelial remodelling after injury |
| Description | Unveiling 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 that initiates a fibrotic cascade in injured lung epithelium. Epithelial-injury-driven enrichment of nuclear transforming growth factor-b-activated kinase 1 (TAK1) mediates EZH2 phosphorylation to facilitate the release of EZH2 from polycomb repressive complex 2 (PRC2). This process leads to the establishment of a fibrotic transcriptional complex of EZH2, RNA-polymerase II (POL2) and nuclear actin, which orchestrates aberrant epithelial lung repair programs. The liberation of EZH2 from PRC2 is accompanied by an EZH2-EZH1 switch to preserve silencing 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. |
| HostingRepository | MassIVE |
| AnnounceDate | 2021-05-04 |
| AnnouncementXML | Submission_2021-05-04_07:47:32.862.xml |
| DigitalObjectIdentifier | |
| ReviewLevel | Non peer-reviewed dataset |
| DatasetOrigin | Original dataset |
| RepositorySupport | Unsupported dataset by repository |
| PrimarySubmitter | Alexandre Rosa Campos |
| SpeciesList | scientific name: Homo sapiens; common name: human; NCBI TaxID: 9606; |
| ModificationList | Oxidation; Acetyl |
| Instrument | Orbitrap Fusion Lumos |
Dataset History
| Revision | Datetime | Status | ChangeLog Entry |
|---|---|---|---|
| 0 | 2021-04-27 23:04:39 | ID requested | |
| ⏵ 1 | 2021-05-04 07:47:33 | announced |
Publication List
| no publication |
Keyword List
| submitter keyword: Actin, EZH2, Lung fibrosis, RNA-polymerase II |
Contact List
| James Peter Garnett | |
|---|---|
| contact affiliation | Boehringer Ingelheim Pharma GmbH |
| contact email | james.garnett@boehringer-ingelheim.com |
| lab head | |
| Alexandre Rosa Campos | |
| contact affiliation | SBP Medical Discovery Institute |
| contact email | arosacampos@sbpdiscovery.org |
| dataset submitter | |
Full Dataset Link List
| MassIVE dataset URI |
| Dataset FTP location NOTE: Most web browsers have now discontinued native support for FTP access within the browser window. But you can usually install another FTP app (we recommend FileZilla) and configure your browser to launch the external application when you click on this FTP link. Or otherwise, launch an app that supports FTP (like FileZilla) and use this address: ftp://massive.ucsd.edu/MSV000087321/ |
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