title: The variant Polycomb Repressor Complex 1 component PCGF1 interacts with a pluripotency sub-network that includes DPPA4, a regulator of embryogenesis.
abstract: PCGF1 encodes one of six human Polycomb RING finger homologs that are linked to transcriptional repression and developmental gene regulation. Individual PCGF proteins define discrete Polycomb Repressor Complex 1 (PRC1) multi-protein complexes with diverse subunit composition whose functions are incompletely understood. PCGF1 is a component of a variant PRC1 complex that also contains the BCL6 co-repressor BCOR and the histone demethylase KDM2B. To further investigate the role of PCGF1, we mapped the physical interactions of the protein under endogenous conditions in a cell model of neuronal differentiation. Using stringent statistical cut-offs, 83 highly enriched interacting proteins were identified, including all previously reported members of the variant PRC1 complex containing PCGF1, as well as proteins linked to diverse cellular pathways such as chromatin and cell cycle regulation. Notably, a sub-network of proteins associated with the establishment and maintenance of pluripotency (NANOG, OCT4, PATZ1, and the developmental regulator DPPA4) were found to independently interact with PCGF1 in a subsequent round of physical interaction mapping experiments. Furthermore, knockdown of PCGF1 results in reduced expression of DPPA4 and other subunits of the variant PRC1 complex at both mRNA and protein levels. Thus, PCGF1 represents a physical and functional link between Polycomb function and pluripotency.
authors.affiliation: School of Biomolecular and Biomedical Science, University College Dublin, Belfield, Dublin 4, IRELAND.
authors.forename: Giorgio
authors.initials: G
authors.lastname: Oliviero
authors.affiliation: School of Biomolecular and Biomedical Science, University College Dublin, Belfield, Dublin 4, IRELAND.
authors.forename: Nayla
authors.initials: N
authors.lastname: Munawar
authors.affiliation: School of Biomolecular and Biomedical Science, University College Dublin, Belfield, Dublin 4, IRELAND.
authors.forename: Ariane
authors.initials: A
authors.lastname: Watson
authors.affiliation: Department of Genetics, Trinity College Dublin, Dublin 2, IRELAND.
authors.forename: Gundula
authors.initials: G
authors.lastname: Streubel
authors.affiliation: School of Biomolecular and Biomedical Science, University College Dublin, Belfield, Dublin 4, IRELAND.
authors.forename: Gwendolyn
authors.initials: G
authors.lastname: Manning
authors.affiliation: Developmental Biology Center, Masonic Cancer Center, and Department of Genetics, Cell Biology, and Development, University of Minnesota, Minneapolis, MN 55455 USA.
authors.forename: Vivian
authors.initials: V
authors.lastname: Bardwell
authors.affiliation: Department of Genetics, Trinity College Dublin, Dublin 2, IRELAND.
authors.forename: Adrian P
authors.initials: AP
authors.lastname: Bracken
authors.affiliation: School of Biomolecular and Biomedical Science, University College Dublin, Belfield, Dublin 4, IRELAND.
authors.forename: Gerard
authors.initials: G
authors.lastname: Cagney
mesh_terms: D002454:Cell Differentiation / Q000235:genetics*; D004268:DNA-Binding Proteins / Q000096:biosynthesis / Q000235:genetics*; D047108:Embryonic Development / Q000235:genetics*; D044783:F-Box Proteins / Q000235:genetics; D018507:Gene Expression Regulation, Developmental; D055785:Gene Knockdown Techniques; D057809:HEK293 Cells; D006657:Histones / Q000235:genetics; D006801:Humans; D056484:Jumonji Domain-Containing Histone Demethylases / Q000235:genetics; D009474:Neurons / Q000378:metabolism; D009687:Nuclear Proteins / Q000235:genetics*; D063150:Polycomb Repressive Complex 1 / Q000096:biosynthesis / Q000235:genetics*; D011518:Proto-Oncogene Proteins / Q000235:genetics; D012097:Repressor Proteins / Q000235:genetics
chemical_list: C411984:BCOR protein, human; D004268:DNA-Binding Proteins; C000611651:DPPA4 protein, human; D044783:F-Box Proteins; D006657:Histones; D009687:Nuclear Proteins; C496334:PCGF1 protein, human; D011518:Proto-Oncogene Proteins; D012097:Repressor Proteins; D056484:Jumonji Domain-Containing Histone Demethylases; C534524:KDM2A protein, human; D063150:Polycomb Repressive Complex 1