A dimeric state for PRC2

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, whi...

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Bibliographic Details
Published in:Nucleic acids research 2014-08, Vol.42 (14), p.9236-9248
Main Authors: Davidovich, Chen, Goodrich, Karen J, Gooding, Anne R, Cech, Thomas R
Format: Article
Language:English
Subjects:
Animals
Humans
Maltose-Binding Proteins - genetics
Molecular Biology - NAR Breakthrough
Polycomb Repressive Complex 2 - chemistry
Polycomb Repressive Complex 2 - genetics
Polycomb Repressive Complex 2 - metabolism
Protein Multimerization
Recombinant Fusion Proteins - isolation & purification
Recombinant Fusion Proteins - metabolism
RNA - metabolism
Sf9 Cells
Spodoptera
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Summary: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.
ISSN:0305-1048
1362-4962
DOI:10.1093/nar/gku540