PXD025552 is an
original dataset announced via ProteomeXchange.
Dataset Summary
Title | A FOXN1 mutation competitively displaces wild-type FOXN1 from higher-order nuclear condensates to cause immunodeficiency |
Description | The transcription factor FOXN1 is a master regulator of thymic epithelial cell development and function. Here we demonstrate that FOXN1 expression is differentially regulated during organogenesis and participates in multi-molecular nuclear condensates essential for the factor's transcriptional activity. FOXN1's C-terminal sequence regulates the diffusion velocity within these aggregates and modulates the binding to proximal gene regulatory regions. These dynamics are significantly altered in a patient's FOXN1 mutant modified in its C-terminal sequence. This mutant is transcriptionally inactive and acts as a dominant negative factor displacing wild-type FOXN1 from condensates and causing athymia and severe lymphopenia in heterozygotes. Expression of the mutated mouse ortholog, Foxn1, selectively impairs mouse thymic epithelial cell (TEC) differentiation, revealing a gene dose dependency for individual TEC subtypes. We have therefore identified the cause for a primary immunodeficiency disease and determined the mechanism by which this FOXN1 gain-of-function mutant mediates its dominant negative effect. |
HostingRepository | PRIDE |
AnnounceDate | 2021-10-29 |
AnnouncementXML | Submission_2021-10-29_06:42:49.574.xml |
DigitalObjectIdentifier | |
ReviewLevel | Peer-reviewed dataset |
DatasetOrigin | Original dataset |
RepositorySupport | Unsupported dataset by repository |
PrimarySubmitter | Philip Charles |
SpeciesList | scientific name: Homo sapiens (Human); NCBI TaxID: 9606; |
ModificationList | monohydroxylated residue |
Instrument | Orbitrap Fusion Lumos |
Dataset History
Revision | Datetime | Status | ChangeLog Entry |
0 | 2021-04-22 00:36:01 | ID requested | |
⏵ 1 | 2021-10-29 06:42:49 | announced | |
Publication List
Dataset with its publication pending |
Keyword List
submitter keyword: Forkhead box N1 transcription factor, immunodeficiency, thymus |
Contact List
Georg Hollander |
contact affiliation | Department of Paediatrics and the Weatherall Institute of Molecular Medicine, University of Oxford, Oxford, United Kingdom. |
contact email | georg.hollander@paediatrics.ox.ac.uk |
lab head | |
Philip Charles |
contact affiliation | University of Oxford |
contact email | philip.charles@ndm.ox.ac.uk |
dataset submitter | |
Full Dataset Link List
Dataset FTP location
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PRIDE project URI |
Repository Record List
[ + ]
[ - ]
- PRIDE
- PXD025552
- Label: PRIDE project
- Name: A FOXN1 mutation competitively displaces wild-type FOXN1 from higher-order nuclear condensates to cause immunodeficiency