Kloet Susan L, Makowski Matthew M, Baymaz H Irem, van Voorthuijsen Lisa, Karemaker Ino D, Santanach Alexandra, Jansen Pascal W T C, Di Croce Luciano, Vermeulen Michiel
Department of Molecular Biology, Faculty of Science, Radboud Institute for Molecular Life Sciences, Radboud University Nijmegen, The Netherlands.
Centre for Genomic Regulation (CRG), The Barcelona Institute of Science and Technology, Barcelona, Spain.
Nat Struct Mol Biol. 2016 Jul;23(7):682-690. doi: 10.1038/nsmb.3248. Epub 2016 Jun 13.
Although the core subunits of Polycomb group (PcG) complexes are well characterized, little is known about the dynamics of these protein complexes during cellular differentiation. We used quantitative interaction proteomics and genome-wide profiling to study PcG proteins in mouse embryonic stem cells (ESCs) and neural progenitor cells (NPCs). We found that the stoichiometry and genome-wide binding of PRC1 and PRC2 were highly dynamic during neural differentiation. Intriguingly, we observed a downregulation and loss of PRC2 from chromatin marked with trimethylated histone H3 K27 (H3K27me3) during differentiation, whereas PRC1 was retained at these sites. Additionally, we found PRC1 at enhancer and promoter regions independently of PRC2 binding and H3K27me3. Finally, overexpression of NPC-specific PRC1 interactors in ESCs led to increased Ring1b binding to, and decreased expression of, NPC-enriched Ring1b-target genes. In summary, our integrative analyses uncovered dynamic PcG subcomplexes and their widespread colocalization with active chromatin marks during differentiation.
尽管多梳蛋白家族（PcG）复合物的核心亚基已得到充分表征，但对于这些蛋白质复合物在细胞分化过程中的动态变化却知之甚少。我们运用定量相互作用蛋白质组学和全基因组分析方法，对小鼠胚胎干细胞（ESCs）和神经祖细胞（NPCs）中的PcG蛋白进行了研究。我们发现，在神经分化过程中，PRC1和PRC2的化学计量和全基因组结合具有高度动态性。有趣的是，我们观察到在分化过程中，PRC2从三甲基化组蛋白H3 K27（H3K27me3）标记的染色质上出现下调和丢失，而PRC1则保留在这些位点。此外，我们发现PRC1在增强子和启动子区域独立于PRC2结合和H3K27me3存在。最后，在ESCs中过表达NPC特异性PRC1相互作用蛋白导致Ring1b与NPC富集的Ring1b靶基因的结合增加，以及这些基因的表达减少。总之，我们的综合分析揭示了动态的PcG亚复合物及其在分化过程中与活性染色质标记的广泛共定位。
