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PXD025552

PXD025552 is an original dataset announced via ProteomeXchange.

Dataset Summary
TitleA FOXN1 mutation competitively displaces wild-type FOXN1 from higher-order nuclear condensates to cause immunodeficiency
DescriptionThe 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.
HostingRepositoryPRIDE
AnnounceDate2021-10-29
AnnouncementXMLSubmission_2021-10-29_06:42:49.574.xml
DigitalObjectIdentifier
ReviewLevelPeer-reviewed dataset
DatasetOriginOriginal dataset
RepositorySupportUnsupported dataset by repository
PrimarySubmitterPhilip Charles
SpeciesList scientific name: Homo sapiens (Human); NCBI TaxID: 9606;
ModificationListmonohydroxylated residue
InstrumentOrbitrap Fusion Lumos
Dataset History
RevisionDatetimeStatusChangeLog Entry
02021-04-22 00:36:01ID requested
12021-10-29 06:42:49announced
Publication List
Dataset with its publication pending
Keyword List
submitter keyword: Forkhead box N1 transcription factor, immunodeficiency, thymus
Contact List
Georg Hollander
contact affiliationDepartment of Paediatrics and the Weatherall Institute of Molecular Medicine, University of Oxford, Oxford, United Kingdom.
contact emailgeorg.hollander@paediatrics.ox.ac.uk
lab head
Philip Charles
contact affiliationUniversity of Oxford
contact emailphilip.charles@ndm.ox.ac.uk
dataset submitter
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