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Updated: Jul 1, 2025

Using the E1A Minigene Tool to Study mRNA Splicing Changes
Published on: April 22, 2021
Alternative splicing decouples local from global PRC2 activity
Niccolò Arecco1, Ivano Mocavini2, Enrique Blanco2
1Systems and Synthetic Biology Unit, Centre for Genomic Regulation (CRG), The Barcelona Institute for Science and Technology, Carrer del Doctor Aiguader 88, Barcelona 08003, Spain.
Abstract:
The Polycomb repressive complex 2 (PRC2) mediates epigenetic maintenance of gene silencing in eukaryotes via methylation of histone H3 at lysine 27 (H3K27). Accessory factors define two distinct subtypes, PRC2.1 and PRC2.2, with different actions and chromatin-targeting mechanisms. The mechanisms orchestrating PRC2 assembly are not fully understood. Here, we report that alternative splicing (AS) of PRC2 core component SUZ12 generates an uncharacterized isoform SUZ12-S, which co-exists with the canonical SUZ12-L isoform in virtually all tissues and developmental stages. SUZ12-S drives PRC2.1 formation and favors PRC2 dimerization. While SUZ12-S is necessary and sufficient for the repression of target genes via promoter-proximal H3K27me3 deposition, SUZ12-L maintains global H3K27 methylation levels. Mouse embryonic stem cells (ESCs) lacking either isoform exit pluripotency more slowly and fail to acquire neuronal cell identity. Our findings reveal a physiological mechanism regulating PRC2 assembly and higher-order interactions in eutherians, with impacts on H3K27 methylation and gene repression.
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