Polycomb repression works without Siesta, the Drosophila ortholog of mammalian PCGF3

TL;DR

This study shows that a Drosophila protein related to a mammalian PRC1 component doesn't help repress genes but affects larval movement, suggesting a need to revise how PRC1 complexes are classified.

Contribution

The study reveals that Siesta, a Drosophila PCGF ortholog, functions independently of Polycomb repression and challenges the role of H2A ubiquitylation in gene silencing.

Findings

Canonical PRC1 and variant RING1 complexes ubiquitylate H2A at distinct genomic regions.

Siesta is not required for repression of developmental genes but controls larval locomotion.

H2A ubiquitylation has minimal impact on transcriptional repression.

Abstract

Polycomb group proteins mediate epigenetic repression via multisubunit complexes, including canonical Polycomb Repressive Complex 1 (PRC1), which monoubiquitylates histone H2A and binds histone H3 trimethylated at lysine-27 (H3K27me3). The RING1 subunit of PRC1, critical for H2A ubiquitylation, forms other complexes. These variant RING1 complexes also ubiquitylate H2A but cannot bind H3K27me3, and their role in epigenetic repression is debated. Using Drosophila genetics, we found that canonical PRC1 and variant RING1 complexes ubiquitylate H2A at distinct genomic regions. We established that the Drosophila PCGF protein specific for variant RING1 complexes, which we named Siesta, is not required for epigenetic repression of developmental genes but controls larval locomotion independently of H2A ubiquitylation. Leveraging a massively parallel transgenic approach, we demonstrated that H2A ubiquitylation has minimal impact on transcriptional repression. Our findings imply that Siesta-RING1 complexes operate outside the Polycomb regulatory system and that the popular PRC1 classification will benefit from revision.

The study of the Drosophila PCGF3 ortholog revisits the PRC1 taxonomy and questions the role of H2AK118 ubiquitylation.

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