PXD053693-1

PXD053693 is an original dataset announced via ProteomeXchange.

Title	Auto-inhibition of PRC2 by the broadly expressed long isoform of AEBP2.
Description	Polycomb Repressive Complex 2 (PRC2) is an essential chromatin regulator responsible for mono-, di- and tri- methylating H3K27. Control of PRC2 activity is a critical process in development and disease. While PRC2 is inhibited in germinal cells, no inhibitory cofactor has been identified in somatic cells. Here we show that the alternative isoforms of its accessory subunit AEBP2, namely AEPB2S (short) and AEBP2L (long), perform opposite functions in modulating PRC2 activity. While AEPB2S is predominantly expressed during early embryogenesis, AEBP2L is expressed throughout embryogenesis and adulthood. AEPB2L inhibits both DNA binding by PRC2 and its histone methyltransferase activity in vitro and impairs PRC2 binding to target genes in embryonic stem cells. In contrast, AEBP2S promotes the DNA-binding activity of PRC2 and is essential for de novo repression of target genes during the transition from naïve to primed pluripotency. Mechanistically, through high-resolution Cryo-EM and mutagenesis, we show that the recently evolved, negatively charged N-terminal region of AEBP2L inhibits PRC2. We propose a model in which the N-terminus of AEPB2L arose in vertebrates to restrain PRC2 in somatic cells.
HostingRepository	PRIDE
AnnounceDate	2025-08-26
AnnouncementXML	Submission_2025-08-26_03:02:24.787.xml
DigitalObjectIdentifier
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Unsupported dataset by repository
PrimarySubmitter	Pascal Jansen
SpeciesList	scientific name: Mus musculus (Mouse); NCBI TaxID: 10090;
ModificationList	acetylated residue; monohydroxylated residue; iodoacetamide derivatized residue
Instrument	Orbitrap Exploris 480

Revision	Datetime	Status	ChangeLog Entry
0	2024-07-05 05:10:53	ID requested
⏵ 1	2025-08-26 03:02:25	announced

Dataset with its publication pending

submitter keyword: Cryo-EM., JARID2, embryonic stem cells, PRC2.2,Polycomb, SUZ12, Trithorax, AEBP2

Adrian P. Bracken
contact affiliation	Smurfit Institute of Genetics, Trinity College Dublin, Dublin, Ireland.
contact email	adrian.bracken@tcd.ie
lab head
Pascal Jansen
contact affiliation	Radboud University
contact email	p.jansen@science.ru.nl
dataset submitter

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PRIDE project URI

• PRIDE
  1. PXD053693
     1. Label: PRIDE project
     2. Name: Auto-inhibition of PRC2 by the broadly expressed long isoform of AEBP2.