9XZI

Crystal Structure of the SUZ12-RBBP4-PHF19-EPOP PRC2.1 Subcomplex

Summary for 9XZI

• Entry DOI: 10.2210/pdb9xzi/pdb
• Descriptor: Polycomb protein SUZ12, Histone-binding protein RBBP4, PHD finger protein 19, ... (5 entities in total)
• Functional Keywords: methyltransferase, transcription, epigenetics
• Biological source: Homo sapiens (human); More
• Total number of polymer chains: 4
• Total formula weight: 119111.60

Authors

Yang, X.,Liu, X. (deposition date: 2025-08-27, release date: 2026-02-11, Last modification date: 2026-02-25)

Primary citation

Gong, L.,Liu, X.,Yang, X.,Yu, Z.,Bhat, M.Y.,Chen, S.,Lemoff, A.,Xing, C.,Liu, X.
EPOP restricts PRC2.1 targeting to chromatin by directly modulating enzyme complex dimerization.
Nat Commun, 17:1565-1565, 2026

PubMed Abstract: Polycomb repressive complex 2 (PRC2) mediates developmental gene repression as two classes of holocomplexes, PRC2.1 and PRC2.2. EPOP is an accessory subunit specific to PRC2.1, which also contains PCL proteins. Unlike other accessory subunits that collectively facilitate PRC2 targeting, EPOP was implicated in an enigmatic inhibitory role, together with its interactor Elongin BC. We report an unusual molecular mechanism whereby EPOP regulates PRC2.1 by directly modulating its oligomerization state. EPOP disrupts the PRC2.1 dimer and weakens its chromatin association, likely by disabling the avidity effect conferred by the dimeric complex. Congruently, an EPOP mutant specifically defective in PRC2 binding enhances genome-wide enrichments of MTF2 in mouse epiblast-like cells. Elongin BC is largely dispensable for the EPOP-mediated inhibition of PRC2.1. EPOP defines a distinct subclass of PRC2.1, which may uniquely maintain an epigenetic program by preventing the over-repression of key gene regulators along the continuum of early differentiation.

PubMed: 41519789
DOI: 10.1038/s41467-025-68280-5

Experimental method

X-RAY DIFFRACTION (2.691 Å)