PXD043672-2

PXD043672 is an original dataset announced via ProteomeXchange.

Title	Pioneer activity distinguishes activating from non-activating SOX2 binding sites
Description	Genome-wide transcriptional activity involves the binding of many transcription factors to thousands of sites in the genome. Determining which sites are directly driving transcription remains a challenge. Here we use acute protein depletion of the pioneer transcription factor SOX2 to establish its functionality in maintaining chromatin accessibility. We show that thousands of accessible sites are lost within an hour of protein depletion, indicating rapid turnover of these sites in the absence of pioneer factors. To understand the relationship with transcription we performed nascent transcription analysis and found that open chromatin sites that are maintained by SOX2 are highly predictive of gene expression, in contrast to all other SOX2 binding sites. We use CRISPR-Cas9 genome editing in the Klf2 locus to functionally validate a predicted regulatory element. We conclude that the regulatory activity of SOX2 is exerted largely at sites where it maintains accessibility and that other binding sites are largely dispensable for gene regulation.
HostingRepository	PRIDE
AnnounceDate	2023-11-14
AnnouncementXML	Submission_2023-11-14_09:12:42.314.xml
DigitalObjectIdentifier
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Unsupported dataset by repository
PrimarySubmitter	Liesbeth Hoekman
SpeciesList	scientific name: Mus musculus (Mouse); NCBI TaxID: 10090;
ModificationList	monohydroxylated residue; iodoacetamide derivatized residue
Instrument	Orbitrap Exploris 480

Revision	Datetime	Status	ChangeLog Entry
0	2023-07-11 05:43:59	ID requested
1	2023-10-24 13:50:35	announced
⏵ 2	2023-11-14 09:12:47	announced	2023-11-14: Updated project metadata.
3	2024-10-22 06:13:18	announced	2024-10-22: Updated project metadata.

Maresca M, van den Brand T, Li H, Teunissen H, Davies J, de Wit E, Pioneer activity distinguishes activating from non-activating SOX2 binding sites. EMBO J, 42(20):e113150(2023) [pubmed]

submitter keyword: SOX2, LC-MSMS, proteomics, chromatin accessibility, gene regulation, acute protein depletion

Onno Bleijerveld
contact affiliation	Proteomics Facility, Netherlands Cancer Institute, Amsterdam, Netherlands
contact email	o.bleijerveld@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/PXD043672

PRIDE project URI

• PRIDE
  1. PXD043672
     1. Label: PRIDE project
     2. Name: Pioneer activity distinguishes activating from non-activating SOX2 binding sites