PXD050685 is an
original dataset announced via ProteomeXchange.
Dataset Summary
Title | Redirecting the pioneering function of FOXA1 with covalent small molecules |
Description | Pioneer 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. |
HostingRepository | PRIDE |
AnnounceDate | 2024-09-05 |
AnnouncementXML | Submission_2024-09-05_15:56:12.530.xml |
DigitalObjectIdentifier | |
ReviewLevel | Peer-reviewed dataset |
DatasetOrigin | Original dataset |
RepositorySupport | Unsupported dataset by repository |
PrimarySubmitter | Sang Joon Won |
SpeciesList | scientific name: Homo sapiens (Human); NCBI TaxID: 9606; |
ModificationList | No PTMs are included in the dataset |
Instrument | Orbitrap Fusion |
Dataset History
Revision | Datetime | Status | ChangeLog Entry |
0 | 2024-03-16 15:50:47 | ID requested | |
⏵ 1 | 2024-09-05 15:56:12 | announced | |
Publication List
Dataset with its publication pending |
Keyword List
submitter keyword: FOXA1, ABPP, cysteine, proteomics, chemical probe |
Contact List
Benjamin F. Cravatt |
contact affiliation | Department of Chemistry, The Scripps Research Institute, USA |
contact email | cravatt@scripps.edu |
lab head | |
Sang Joon Won |
contact affiliation | The Scripps Research Institute |
contact email | swon@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
[ + ]
[ - ]
- PRIDE
- PXD050685
- Label: PRIDE project
- Name: Redirecting the pioneering function of FOXA1 with covalent small molecules