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PXD036589

PXD036589 is an original dataset announced via ProteomeXchange.

Dataset Summary
TitlePPARγ lipodystrophy mutants reveal intermolecular interactions required for enhancer activation
DescriptionThe peroxisome proliferator-activated receptor γ (PPARγ) is the master regulator of adipocyte differentiation, and mutations that interfere with PPARγ function cause lipodystrophy. Structural studies indicate that PPARγ domains engage in several intra- and inter-moleuclar interactions; however, how these interactions modulate the ability of PPARγ to activate target genes in a cellular context is currently poorly understood. Here we analysed the transcriptional potential of R212Q and E379K two previously uncharacterised lipodystrophy-associated PPARγ mutants that are located in distinct PPARγ domains but are both predicted to affect intermolecular interactions. Using a combination of biochemical and genome-wide approaches we show that these mutations impair binding to an overlapping subset of enhancers that are less accessible and specifically require PPARγ for chromatin remodeling. Based on these findings we propose a model in which recruitment of PPARγ to chromatin is determined by several intermolecular interfaces. Furthermore, our data exemplify that relatively subtle molecular defects in transcription factors are sufficient to significantly affect enhancer binding and thereby transcriptional output.
HostingRepositoryPRIDE
AnnounceDate2022-09-08
AnnouncementXMLSubmission_2022-09-08_07:21:45.333.xml
DigitalObjectIdentifier
ReviewLevelPeer-reviewed dataset
DatasetOriginOriginal dataset
RepositorySupportUnsupported dataset by repository
PrimarySubmitterPascal Jansen
SpeciesList scientific name: Homo sapiens (Human); NCBI TaxID: 9606;
ModificationListacetylated residue; monohydroxylated residue; iodoacetamide derivatized residue
InstrumentOrbitrap Exploris 480
Dataset History
RevisionDatetimeStatusChangeLog Entry
02022-09-08 07:09:53ID requested
12022-09-08 07:21:45announced
Publication List
Dataset with its publication pending
Keyword List
submitter keyword: Human, adipocyte differentiation, PPARg
Contact List
Eric Kalkhoven
contact affiliationCenter for Molecular Medicine, University Medical Center Utrecht, Utrecht University, Utrecht, The Netherlands.
contact emailE.Kalkhoven@umcutrecht.nl
lab head
Pascal Jansen
contact affiliationRadboud University
contact emailp.jansen@science.ru.nl
dataset submitter
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Dataset FTP location
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