<<< Full experiment listing

PXD050685

PXD050685 is an original dataset announced via ProteomeXchange.

Dataset Summary
TitleRedirecting the pioneering function of FOXA1 with covalent small molecules
DescriptionPioneer transcription factors (TFs) exhibit a special ability to bind to and open closed chromatin, facilitating engagement by other regulatory factors involved in gene activation or repression. Chemical probes are lacking for pioneer TFs, which has hindered their mechanistic investigation in cells. Here, we report electrophilic small molecules that stereoselectively and site-specifically bind the pioneer TF, FOXA1, at a cysteine (C258) within the forkhead DNA-binding domain. We show that these covalent ligands react with FOXA1 in a DNA-dependent manner and rapidly remodel its pioneer activity in prostate cancer cells reflected in redistribution of FOXA1 binding across the genome and directionally correlated changes in chromatin accessibility. Motif analysis supports a mechanism where the covalent ligands relax the canonical DNA binding preference of FOXA1 by strengthening interactions with suboptimal ancillary sequences in predicted proximity to C258. Our findings reveal a striking plasticity underpinning the pioneering function of FOXA1 that can be controlled by small molecules.
HostingRepositoryPRIDE
AnnounceDate2024-09-05
AnnouncementXMLSubmission_2024-09-05_15:56:12.530.xml
DigitalObjectIdentifier
ReviewLevelPeer-reviewed dataset
DatasetOriginOriginal dataset
RepositorySupportUnsupported dataset by repository
PrimarySubmitterSang Joon Won
SpeciesList scientific name: Homo sapiens (Human); NCBI TaxID: 9606;
ModificationListNo PTMs are included in the dataset
InstrumentOrbitrap Fusion
Dataset History
RevisionDatetimeStatusChangeLog Entry
02024-03-16 15:50:47ID requested
12024-09-05 15:56:12announced
Publication List
Dataset with its publication pending
Keyword List
submitter keyword: FOXA1, ABPP, cysteine, proteomics, chemical probe
Contact List
Benjamin F. Cravatt
contact affiliationDepartment of Chemistry, The Scripps Research Institute, USA
contact emailcravatt@scripps.edu
lab head
Sang Joon Won
contact affiliationThe Scripps Research Institute
contact emailswon@scripps.edu
dataset submitter
Full Dataset Link List
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/2024/09/PXD050685
PRIDE project URI
Repository Record List
[ + ]