Hauri Simon, Comoglio Federico, Seimiya Makiko, Gerstung Moritz, Glatter Timo, Hansen Klaus, Aebersold Ruedi, Paro Renato, Gstaiger Matthias, Beisel Christian
Department of Biology, Institute of Molecular Systems Biology, ETH Zürich, 8093 Zürich, Switzerland; Competence Center Personalized Medicine UZH/ETH, 8044 Zürich, Switzerland.
Department of Biosystems Science and Engineering, ETH Zürich, 4058 Basel, Switzerland.
Cell Rep. 2016 Oct 4;17(2):583-595. doi: 10.1016/j.celrep.2016.08.096.
Polycomb group (PcG) proteins are major determinants of gene silencing and epigenetic memory in higher eukaryotes. Here, we systematically mapped the human PcG complexome using a robust affinity purification mass spectrometry approach. Our high-density protein interaction network uncovered a diverse range of PcG complexes. Moreover, our analysis identified PcG interactors linking them to the PcG system, thus providing insight into the molecular function of PcG complexes and mechanisms of recruitment to target genes. We identified two human PRC2 complexes and two PR-DUB deubiquitination complexes, which contain the O-linked N-acetylglucosamine transferase OGT1 and several transcription factors. Finally, genome-wide profiling of PR-DUB components indicated that the human PR-DUB and PRC1 complexes bind distinct sets of target genes, suggesting differential impact on cellular processes in mammals.
多梳蛋白家族（PcG）蛋白是高等真核生物中基因沉默和表观遗传记忆的主要决定因素。在此，我们使用一种强大的亲和纯化质谱方法系统地绘制了人类PcG复合物组图谱。我们的高密度蛋白质相互作用网络揭示了多种不同的PcG复合物。此外，我们的分析确定了将PcG复合物与PcG系统联系起来的相互作用蛋白，从而深入了解了PcG复合物的分子功能以及招募到靶基因的机制。我们鉴定出两种人类PRC2复合物和两种PR-DUB去泛素化复合物，它们包含O-连接的N-乙酰葡糖胺转移酶OGT1和几种转录因子。最后，对PR-DUB组分的全基因组分析表明，人类PR-DUB和PRC1复合物结合不同的靶基因集，这表明它们对哺乳动物细胞过程有不同的影响。
