PXD038902

PXD038902 is an original dataset announced via ProteomeXchange.

Title	PAXIP1 and STAG2 converge to maintain 3D genome archi-tecture and facilitate promoter/enhancer contacts to enable stress hormone-dependent transcription
Description	How steroid hormone receptors (SHRs) orchestrate transcriptional activity remains only partly understood. Upon activation, SHRs bind the genome and recruit their co-regulators, crucial to induce gene expression. However, it remains unknown which components of the SHR-recruited coregulator complex are essential to drive transcription following hormonal stimuli. Through a FACS-based genome-wide CRISPR screen, we comprehensively dissected the Glucocorticoid Receptor (GR) co-regulatory complex involved in gene-target regulation. We describe a novel functional cross-talk between PAXIP1 and the cohesin subunit STAG2 that is critical for regulation of gene expression by GR. Without altering the GR cistrome, PAXIP1 and STAG2 depletion alter the GR transcriptome, by impairing the recruitment of 3D-genome organization proteins to the GR complex. Importantly, we demonstrate that PAXIP1 is required for stability of cohesin on the genome, its localization to GR-occupied sites, and maintenance of enhancer-promoter interactions. Moreover, in lung cancer, where GR acts as tumor suppressor, PAXIP1/STAG2 loss enhances GR-mediated tumor suppressor activity by modifying local chromatin interactions. All together, we introduce PAXIP1 and STAG2 as novel co-regulators of GR, required to maintain 3D-genome architecture and drive the GR transcriptional programme following hormonal stimuli.
HostingRepository	PRIDE
AnnounceDate	2023-11-14
AnnouncementXML	Submission_2023-11-14_09:08:34.675.xml
DigitalObjectIdentifier
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Unsupported dataset by repository
PrimarySubmitter	Liesbeth Hoekman
SpeciesList	scientific name: Homo sapiens (Human); NCBI TaxID: 9606;
ModificationList	deamidated residue; iodoacetamide derivatized residue
Instrument	Orbitrap Exploris 480; Orbitrap Fusion

Revision	Datetime	Status	ChangeLog Entry
0	2022-12-19 03:01:09	ID requested
1	2023-10-24 11:59:41	announced
⏵ 2	2023-11-14 09:08:35	announced	2023-11-14: Updated project metadata.

Mayayo-Peralta I, Gregoricchio S, Schuurman K, Yavuz S, Zaalberg A, Kojic A, Abbott N, Geverts B, Beerthuijzen S, Siefert J, Severson TM, van Baalen M, Hoekman L, Lieftink C, Altelaar M, Beijersbergen RL, Houtsmuller AB, Prekovic S, Zwart W, PAXIP1 and STAG2 converge to maintain 3D genome architecture and facilitate promoter/enhancer contacts to enable stress hormone-dependent transcription. Nucleic Acids Res, 51(18):9576-9593(2023) [pubmed]

submitter keyword: LC-MSMS

PAXIP1

STAG2

RIME;Glucocorticoid receptor;

Maarten Altelaar
contact affiliation	Proteomics Facility, The Netherlands Cancer Institute, Amsterdam, The Netherlands; Biomolecular Mass Spectrometry and Proteomics, Bijvoet Center for Biomolecular Re-search, Utrecht Institute for Pharmaceutical Sciences, Utrecht University and Netherlands Proteomics Centre, Utrecht, The Netherlands
contact email	m.altelaar@nki.nl
lab head
Liesbeth Hoekman
contact affiliation	The Netherlands Cancer Institute, Amsterdam, The Netherlands.
contact email	l.hoekman@nki.nl
dataset submitter

Dataset FTP location NOTE: Most web browsers have now discontinued native support for FTP access within the browser window. But you can usually install another FTP app (we recommend FileZilla) and configure your browser to launch the external application when you click on this FTP link. Or otherwise, launch an app that supports FTP (like FileZilla) and use this address: ftp://ftp.pride.ebi.ac.uk/pride/data/archive/2023/10/PXD038902

PRIDE project URI

• PRIDE
  1. PXD038902
     1. Label: PRIDE project
     2. Name: PAXIP1 and STAG2 converge to maintain 3D genome archi-tecture and facilitate promoter/enhancer contacts to enable stress hormone-dependent transcription