title: Binding of the RING polycomb proteins to specific target genes in complex with the grainyhead-like family of developmental transcription factors.
abstract: The Polycomb group (PcG) of proteins represses homeotic gene expression through the assembly of multiprotein complexes on key regulatory elements. The mechanisms mediating complex assembly have remained enigmatic since most PcG proteins fail to bind DNA. We now demonstrate that the human PcG protein dinG interacts with CP2, a mammalian member of the grainyhead-like family of transcription factors, in vitro and in vivo. The functional consequence of this interaction is repression of CP2-dependent transcription. The CP2-dinG interaction is conserved in evolution with the Drosophila factor grainyhead binding to dring, the fly homologue of dinG. Electrophoretic mobility shift assays demonstrate that the grh-dring complex forms on regulatory elements of genes whose expression is repressed by grh but not on elements where grh plays an activator role. These observations reveal a novel mechanism by which PcG proteins may be anchored to specific regulatory elements in developmental genes.
authors.affiliation: Rotary Bone Marrow Research Laboratory, Royal Melbourne Hospital Research Foundation, c/o RMH Post Office, Grattan Street, Parkville, Victoria 3050, Australia.
authors.forename: Annabel
authors.initials: A
authors.lastname: Tuckfield
authors.forename: David R
authors.initials: DR
authors.lastname: Clouston
authors.forename: Tomasz M
authors.initials: TM
authors.lastname: Wilanowski
authors.forename: Lin-Lin
authors.initials: LL
authors.lastname: Zhao
authors.forename: John M
authors.initials: JM
authors.lastname: Cunningham
authors.forename: Stephen M
authors.initials: SM
authors.lastname: Jane
mesh_terms: D020816:Amino Acid Motifs / Q000502:physiology; D000818:Animals; D001665:Binding Sites / Q000502:physiology; D018797:Cell Cycle Proteins; D004268:DNA-Binding Proteins / Q000235:genetics / Q000378:metabolism*; D004330:Drosophila; D029721:Drosophila Proteins / Q000378:metabolism; D005656:Fungal Proteins / Q000378:metabolism; D015723:Gene Library; D005982:Glutathione Transferase / Q000235:genetics; D006801:Humans; D020014:K562 Cells; D046911:Macromolecular Substances; D008969:Molecular Sequence Data; D046912:Multiprotein Complexes; D063150:Polycomb Repressive Complex 1; D011485:Protein Binding / Q000502:physiology; D017434:Protein Structure, Tertiary / Q000502:physiology; D016601:RNA-Binding Proteins; D011993:Recombinant Fusion Proteins / Q000235:genetics / Q000378:metabolism; D012097:Repressor Proteins / Q000494:pharmacology; D029701:Saccharomyces cerevisiae Proteins; D017386:Sequence Homology, Amino Acid; D015534:Trans-Activators; D014157:Transcription Factors / Q000235:genetics / Q000378:metabolism*; D015533:Transcriptional Activation / Q000187:drug effects; D020798:Two-Hybrid System Techniques; D044767:Ubiquitin-Protein Ligases; D016335:Zinc Fingers
chemical_list: D018797:Cell Cycle Proteins; D004268:DNA-Binding Proteins; D029721:Drosophila Proteins; D005656:Fungal Proteins; C077306:HPC2 protein, S cerevisiae; D046911:Macromolecular Substances; D046912:Multiprotein Complexes; D016601:RNA-Binding Proteins; D011993:Recombinant Fusion Proteins; D012097:Repressor Proteins; D029701:Saccharomyces cerevisiae Proteins; D015534:Trans-Activators; D014157:Transcription Factors; C062330:grh protein, Drosophila; D063150:Polycomb Repressive Complex 1; C080355:RING1 protein, human; C489841:RNF2 protein, human; D044767:Ubiquitin-Protein Ligases; D005982:Glutathione Transferase