2025-09-09 理化学研究所
本研究で明らかにしたポリコム複合体PCGF1-PRC1による転写抑制解除機構の概要
<関連情報>
- https://www.riken.jp/press/2025/20250909_2/index.html
- https://www.cell.com/molecular-cell/fulltext/S1097-2765(25)00654-9
ポリコム複合体によって沈黙化された遺伝子に結合したSKP1AはPRC2の分解を媒介し、その活性化を事前条件付ける SKP1A bound to Polycomb-silenced genes mediates degradation of PRC2 and preconditions their activation
Takashi Kondo ∙ Shinsuke Ito ∙ Junichiro Takano ∙ … ∙ Osamu Ohara ∙ Manabu Nakayama ∙ Haruhiko Koseki
Molecular Cell Published:August 25, 2025
DOI:https://doi.org/10.1016/j.molcel.2025.08.004
Highlights
- PCGF1-PRC1 associates with SKP1A to regulate the CGI proteome
- SKP1A degrades EED on CGIs to activate repressed genes
- Proteasomal activity is involved in regulation of developmental genes
Summary
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.
