PXD042735-1

PXD042735 is an original dataset announced via ProteomeXchange.

Title	KDM3A and KDM3B Maintain Naïve Pluripotency Through the Regulation of Alternative Splicing
Description	Histone modifying enzymes play a central role in maintaining cell identity by establishing a conducive chromatin environment for lineage specific transcription factor activity. Pluripotent embryonic stem cells (ESCs) identity is characterized by lower abundance of gene repression associated histone modifications that enables rapid response to differentiation cues. The KDM3 histone demethylase family removes the repressive histone H3 lysine 9 dimethylation (H3K9me2). Here we uncover a surprising role for the KDM3 proteins in the maintenance of the pluripotent state through post-transcriptional regulation. We find through immunoaffinity purification of the KDM3A or KDM3B interactome and proximity ligation assays that KDM3A and KDM3B interact with RNA processing factors such as EFTUD2 and PRMT5. By generating double “degron” ESCs to degrade KDM3A and KDM3B in the rapid timescale of splicing, we find altered splicing, independent of H3K9me2 status. These splicing changes partially resemble the splicing pattern of the more blastocyst-like ground state of pluripotency and occurred in important chromatin and transcription factors such as Dnmt3b, Tbx3 and Tcf12. Our findings reveal non-canonical roles of histone modifying enzymes in splicing to regulate cell identity.
HostingRepository	PRIDE
AnnounceDate	2025-06-23
AnnouncementXML	Submission_2025-06-22_16:04:06.405.xml
DigitalObjectIdentifier	https://dx.doi.org/10.6019/PXD042735
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Supported dataset by repository
PrimarySubmitter	Caleb Dillingham
SpeciesList	scientific name: Mus musculus (Mouse); NCBI TaxID: 10090;
ModificationList	No PTMs are included in the dataset
Instrument	LTQ Orbitrap Elite

Revision	Datetime	Status	ChangeLog Entry
0	2023-06-05 12:06:21	ID requested
⏵ 1	2025-06-22 16:04:07	announced

10.6019/PXD042735;

10.1016/j.isci.2025.112612;

Dillingham CM, Cormaty H, Morgan EC, Tak AI, Esgdaille DE, Boutz PL, Sridharan R, KDM3A and KDM3B regulate alternative splicing in mouse pluripotent stem cells. iScience, 28(6):112612(2025) [pubmed]

submitter keyword: FLAG-IP,mESCs, histone demethylases

Rupa Sridharan
contact affiliation	University of Wisconsin-Madison, Cellular and Regenerative Medicine
contact email	rsridharan2@wisc.edu
lab head
Caleb Dillingham
contact affiliation	University of Wisconsin-Madison
contact email	cdillingham@wisc.edu
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/2025/06/PXD042735

PRIDE project URI

• PRIDE
  1. PXD042735
     1. Label: PRIDE project
     2. Name: KDM3A and KDM3B Maintain Naïve Pluripotency Through the Regulation of Alternative Splicing