| First Author | Kondo T | Year | 2025 |
| Journal | Mol Cell | Volume | 85 |
| Issue | 17 | Pages | 3306-3320.e6 |
| PubMed ID | 40858113 | Mgi Jnum | J:372344 |
| Mgi Id | MGI:8247504 | Doi | 10.1016/j.molcel.2025.08.004 |
| Citation | Kondo T, et al. (2025) SKP1A bound to Polycomb-silenced genes mediates degradation of PRC2 and preconditions their activation. Mol Cell 85(17):3306-3320.e6 |
| abstractText | Polycomb group (PcG) proteins are repressors of developmental genes. Paradoxically, the same PcG proteins also function in gene activation via mechanisms that are not yet fully understood. Here, we found that SKP1A, an essential factor of SKP1A/CUL1/F-box (SCF) ubiquitin ligases and Polycomb-repressive complex 1 (PRC1) containing PCGF1 (PCGF1-PRC1), mediates the link between PcG-dependent gene regulation and ubiquitin proteasomal degradation. By using differentiating mouse embryonic stem cells and the midbrain of developing mouse embryos, we found that SKP1A removes EED, a core component of PRC2 that is bound to PcG-target-gene promoters, via proteasomal degradation, and it thereby sensitizes these genes for subsequent activation. In summary, we reveal here a previously unknown role of SKP1A in preconditioning activation of PcG-target genes via the proteasomal degradation of PRC2. This indicates that SKP1A-containing PCGF1-PRC1 may contribute to confer reversibility on PcG-mediated gene silencing for spatiotemporal regulation of target genes. |
