PXD036589 is an
original dataset announced via ProteomeXchange.
Dataset Summary
Title | PPARγ lipodystrophy mutants reveal intermolecular interactions required for enhancer activation |
Description | The 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. |
HostingRepository | PRIDE |
AnnounceDate | 2022-09-08 |
AnnouncementXML | Submission_2022-09-08_07:21:45.333.xml |
DigitalObjectIdentifier | |
ReviewLevel | Peer-reviewed dataset |
DatasetOrigin | Original dataset |
RepositorySupport | Unsupported dataset by repository |
PrimarySubmitter | Pascal Jansen |
SpeciesList | scientific name: Homo sapiens (Human); NCBI TaxID: 9606; |
ModificationList | acetylated residue; monohydroxylated residue; iodoacetamide derivatized residue |
Instrument | Orbitrap Exploris 480 |
Dataset History
Revision | Datetime | Status | ChangeLog Entry |
0 | 2022-09-08 07:09:53 | ID requested | |
⏵ 1 | 2022-09-08 07:21:45 | announced | |
Publication List
Dataset with its publication pending |
Keyword List
submitter keyword: Human, adipocyte differentiation, PPARg |
Contact List
Eric Kalkhoven |
contact affiliation | Center for Molecular Medicine, University Medical Center Utrecht, Utrecht University, Utrecht, The Netherlands. |
contact email | E.Kalkhoven@umcutrecht.nl |
lab head | |
Pascal Jansen |
contact affiliation | Radboud University |
contact email | p.jansen@science.ru.nl |
dataset submitter | |
Full Dataset Link List
Dataset FTP location
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PRIDE project URI |
Repository Record List
[ + ]
[ - ]
- PRIDE
- PXD036589
- Label: PRIDE project
- Name: PPARγ lipodystrophy mutants reveal intermolecular interactions required for enhancer activation