PXD036589

PXD036589 is an original dataset announced via ProteomeXchange.

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

Revision	Datetime	Status	ChangeLog Entry
0	2022-09-08 07:09:53	ID requested
⏵ 1	2022-09-08 07:21:45	announced

Dataset with its publication pending

submitter keyword: Human, adipocyte differentiation, PPARg

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

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PRIDE project URI

• PRIDE
  1. PXD036589
     1. Label: PRIDE project
     2. Name: PPARγ lipodystrophy mutants reveal intermolecular interactions required for enhancer activation