SUMO RNAi-mediated hyper-clustering of PRC1 results in the re-wiring of genome-wide TADs.

Non programmé
20m
amphithéâtre (GENOPOLYS)

amphithéâtre

GENOPOLYS

Génopolys - Campus Arnaud de Villeneu, 34396, 141 Rue de la Cardonille, 34090 Montpellier

Orateur

Nazli AKILLI

Description

Polycomb group complexes (PcGs) are crucial regulators of genome organization in Drosophila, with PRC1—comprised of the subunits Pc, Ph, Psc, and Sce—playing an important role. PRC1 is integral to three-dimensional (3D) chromatin architecture and interacts with PRC2, which mediates the H3K27me3 mark. The clustering of PRC1 into foci, measuring 100 to 200 nm, is closely linked to its functional role in genome organization. Previous studies using RNA interference (RNAi) have shown that nuclear SUMO depletion leads to the formation of large PRC1 foci. Our investigation evaluates how PRC1 hyper-clustering affects its functions through techniques such as Hi-C, RNA sequencing (RNA-seq), and CUT&RUN. Our results indicate that SUMO RNAi reorganizes chromatin without altering H3K27me3 or H3K27ac levels. Additionally, analysis of a SUMO-deficient Pc mutant (Pc-3KR) revealed significant PRC1 clustering and alterations in chromatin organization. Our research demonstrates a strong correlation between changes in chromatin loops, topologically associating domains (TADs), inter-TAD contacts, and transcriptional regulation. This study highlights the essential role of chromatin organization in gene regulation and provides compelling evidence for a novel mechanism of 3D genome modulation that operates independently of established chromatin marks.

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