PXD077002-1

PXD077002 is an original dataset announced via ProteomeXchange.

Title	NAT10-dependent N4-acetylcytidine (ac4C) reprograms R-loops and promotes cancer stem cell growth
Description	R-loop remodeling dynamically regulates chromatin states and gene expression; however, its exploitation by cancer to sustain self-renewal and malignancy remains poorly understood. Here, we found that glioblastoma (GBM) stem cells (GSCs) display highly active R-loops compared to differentiated tumor progeny and neural stem cells (NSCs). Genome-wide mapping by R-loop RNA chromatin immunoprecipitation sequencing (RR-ChIP-seq) revealed cell-specific enrichment and spatial accumulation of R-loops at promoter-proximal regions in GSCs, correlating with active transcription and open chromatin states. We profiled R-loop interactomes and identified N-Acetyltransferase 10 (NAT10), an RNA N4-acetylcytidine (ac4C)-modifying enzyme, as a high-affinity R-loop-binding protein in GSCs. Driven by transcriptional activation via OLIG1, NAT10 was overexpressed in GSCs. ac4C-specific RNA immunoprecipitation sequencing (ac4C-RIP-seq) on R-loop RNA revealed genome-wide mapping of ac4C-modified R-loops with abundant ac4C-modified R-loops that regulated the genome. NAT10 catalyzed widespread ac4C deposition on the RNA stand of R-loops, stabilizing promoter-associated R-loops, and facilitating open chromatin to sustain self-renewal through core stemness regulators, including transcription factor EGR1. NAT10 knockdown suppressed proliferation and maintenance in vitro and attenuated tumor growth in vivo. Pharmacological inhibition of NAT10/ac4C-modified R-loops using the small-molecule inhibitor remodelin phenocopied NAT10 genetic targeting, demonstrating therapeutic promise for targeting cancer.
HostingRepository	PRIDE
AnnounceDate	2026-04-10
AnnouncementXML	Submission_2026-04-10_15:55:30.884.xml
DigitalObjectIdentifier
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Unsupported dataset by repository
PrimarySubmitter	Weichi Wu
SpeciesList	scientific name: Homo sapiens (Human); NCBI TaxID: NEWT:9606;
ModificationList	No PTMs are included in the dataset
Instrument	autoflex

Revision	Datetime	Status	ChangeLog Entry
0	2026-04-10 11:56:15	ID requested
⏵ 1	2026-04-10 15:55:31	announced

Dataset with its publication pending

submitter keyword: ac4C, Cancer stem cell, NAT10, Glioblastoma,R-loop remodeling, Glioblastoma stem cell

Jeremy Naftali Rich
contact affiliation	University of North Carolina, Chapel Hill
contact email	drjeremyrich@gmail.com
lab head
Weichi Wu
contact affiliation	Lineberger Comprehensive Cancer Center, University of North Carolina, Chapel Hill, NC, USA
contact email	wuweichi@hotmail.com
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/2026/04/PXD077002

PRIDE project URI

• PRIDE
  1. PXD077002
     1. Label: PRIDE project
     2. Name: NAT10-dependent N4-acetylcytidine (ac4C) reprograms R-loops and promotes cancer stem cell growth