title: A High-Density Map for Navigating the Human Polycomb Complexome.
abstract: 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.
authors.affiliation: Department of Biology, Institute of Molecular Systems Biology, ETH Zürich, 8093 Zürich, Switzerland; Competence Center Personalized Medicine UZH/ETH, 8044 Zürich, Switzerland.
authors.forename: Simon
authors.initials: S
authors.lastname: Hauri
authors.affiliation: Department of Biosystems Science and Engineering, ETH Zürich, 4058 Basel, Switzerland.
authors.forename: Federico
authors.initials: F
authors.lastname: Comoglio
authors.affiliation: Department of Biosystems Science and Engineering, ETH Zürich, 4058 Basel, Switzerland.
authors.forename: Makiko
authors.initials: M
authors.lastname: Seimiya
authors.affiliation: Department of Biosystems Science and Engineering, ETH Zürich, 4058 Basel, Switzerland.
authors.forename: Moritz
authors.initials: M
authors.lastname: Gerstung
authors.affiliation: Department of Biology, Institute of Molecular Systems Biology, ETH Zürich, 8093 Zürich, Switzerland.
authors.forename: Timo
authors.initials: T
authors.lastname: Glatter
authors.affiliation: Biotech Research and Innovation Centre (BRIC) and Centre for Epigenetics, University of Copenhagen, 2200 Copenhagen, Denmark.
authors.forename: Klaus
authors.initials: K
authors.lastname: Hansen
authors.affiliation: Department of Biology, Institute of Molecular Systems Biology, ETH Zürich, 8093 Zürich, Switzerland; Faculty of Science, University of Zürich, 8057 Zürich, Switzerland.
authors.forename: Ruedi
authors.initials: R
authors.lastname: Aebersold
authors.affiliation: Department of Biosystems Science and Engineering, ETH Zürich, 4058 Basel, Switzerland; Faculty of Sciences, University of Basel, 4056 Basel, Switzerland.
authors.forename: Renato
authors.initials: R
authors.lastname: Paro
authors.affiliation: Department of Biology, Institute of Molecular Systems Biology, ETH Zürich, 8093 Zürich, Switzerland; Competence Center Personalized Medicine UZH/ETH, 8044 Zürich, Switzerland. Electronic address: matthias.gstaiger@imsb.biol.ethz.ch.
authors.forename: Matthias
authors.initials: M
authors.lastname: Gstaiger
authors.affiliation: Department of Biosystems Science and Engineering, ETH Zürich, 4058 Basel, Switzerland. Electronic address: christian.beisel@bsse.ethz.ch.
authors.forename: Christian
authors.initials: C
authors.lastname: Beisel
mesh_terms: D002843:Chromatin / Q000235:genetics; D004268:DNA-Binding Proteins / Q000235:genetics / Q000378:metabolism; D044127:Epigenesis, Genetic / Q000235:genetics; D020868:Gene Silencing; D015894:Genome, Human; D057809:HEK293 Cells; D006657:Histones / Q000235:genetics; D006801:Humans; D013058:Mass Spectrometry; D017351:N-Acetylglucosaminyltransferases / Q000235:genetics* / Q000378:metabolism; D063150:Polycomb Repressive Complex 1 / Q000235:genetics* / Q000378:metabolism; D063151:Polycomb Repressive Complex 2 / Q000235:genetics* / Q000378:metabolism; D063146:Polycomb-Group Proteins / Q000235:genetics* / Q000378:metabolism; D054875:Ubiquitination / Q000235:genetics
chemical_list: D002843:Chromatin; D004268:DNA-Binding Proteins; D006657:Histones; D063146:Polycomb-Group Proteins; D063151:Polycomb Repressive Complex 2; D063150:Polycomb Repressive Complex 1; D017351:N-Acetylglucosaminyltransferases; C063057:UDP-N-acetylglucosamine-peptide beta-N-acetylglucosaminyltransferase
keywords: AP-MS; Polycomb; epigenetics; gene silencing; proteomics