A High Density Map for Navigating the Human Polycomb Complexome

Polycomb group (PcG) proteins are major determinants of gene silencing and epigenetic memory in higher eukaryotes. Here, we used a robust affinity purification mass spectrometry (AP-MS) approach to systematically map the human PcG protein interactome, uncovering an unprecedented breadth of PcG complexes. The obtained high density protein interaction data identified new modes of combinatorial PcG complex formation with proteins previously not associated with the PcG system, thus providing new insights into their molecular function and recruitment mechanisms to target genes. Importantly, we identified two human PR-DUB de-ubiquitination complexes, which comprise the O-linked N-acetylglucosamine transferase OGT1 and a number of transcription factors. By further mapping chromatin binding of PR-DUB components genome-wide, we conclude that the human PR-DUB and PRC1 complexes bind distinct sets of target genes and impact on different cellular processes in mammals.