Kahn, T.G., Garrido, A., Yushkova, A., Kim, M., Glotov, A., Sreekumar, S., Larsson, J., Schwartz, Y.B. (2026). Polycomb repression works without Siesta, the Drosophila ortholog of mammalian PCGF3.  Sci. Adv. 12(10): eaec0733.

FBrf0264828

Research paper

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.

PMC12965321 (PMC) (EuropePMC)