title: A dimeric state for PRC2.
abstract: Polycomb repressive complex-2 (PRC2) is a histone methyltransferase required for epigenetic silencing during development and cancer. Long non-coding RNAs (lncRNAs) can recruit PRC2 to chromatin. Previous studies identified PRC2 subunits in a complex with the apparent molecular weight of a dimer, which might be accounted for by the incorporation of additional protein subunits or RNA rather than PRC2 dimerization. Here we show that reconstituted human PRC2 is in fact a dimer, using multiple independent approaches including analytical size exclusion chromatography (SEC), SEC combined with multi-angle light scattering and co-immunoprecipitation of differentially tagged subunits. Even though it contains at least two RNA-binding subunits, each PRC2 dimer binds only one RNA molecule. Yet, multiple PRC2 dimers bind a single RNA molecule cooperatively. These observations suggest a model in which the first RNA binding event promotes the recruitment of multiple PRC2 complexes to chromatin, thereby nucleating repression.
authors.affiliation: Department of Chemistry & Biochemistry, Howard Hughes Medical Institute, University of Colorado BioFrontiers Institute, Boulder, CO 80309-0596, USA.
authors.forename: Chen
authors.initials: C
authors.lastname: Davidovich
authors.affiliation: Department of Chemistry & Biochemistry, Howard Hughes Medical Institute, University of Colorado BioFrontiers Institute, Boulder, CO 80309-0596, USA.
authors.forename: Karen J
authors.initials: KJ
authors.lastname: Goodrich
authors.affiliation: Department of Chemistry & Biochemistry, Howard Hughes Medical Institute, University of Colorado BioFrontiers Institute, Boulder, CO 80309-0596, USA.
authors.forename: Anne R
authors.initials: AR
authors.lastname: Gooding
authors.affiliation: Department of Chemistry & Biochemistry, Howard Hughes Medical Institute, University of Colorado BioFrontiers Institute, Boulder, CO 80309-0596, USA thomas.cech@colorado.edu.
authors.forename: Thomas R
authors.initials: TR
authors.lastname: Cech
mesh_terms: D000818:Animals; D006801:Humans; D058619:Maltose-Binding Proteins / Q000235:genetics; D063151:Polycomb Repressive Complex 2 / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D055503:Protein Multimerization; D012313:RNA / Q000378:metabolism; D011993:Recombinant Fusion Proteins / Q000302:isolation & purification / Q000378:metabolism; D061987:Sf9 Cells; D018411:Spodoptera
chemical_list: D058619:Maltose-Binding Proteins; D011993:Recombinant Fusion Proteins; D012313:RNA; D063151:Polycomb Repressive Complex 2