A dimeric state for PRC2

Chen Davidovich, Karen J Goodrich, Anne R Gooding, Thomas R Cech

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16 Citations (Scopus)

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.
Original languageEnglish
Article numbergku540
Pages (from-to)9236-9248
Number of pages13
JournalNucleic Acids Research
Volume42
Issue number14
DOIs
Publication statusPublished - 18 Aug 2014
Externally publishedYes

Cite this

Davidovich, C., Goodrich, K. J., Gooding, A. R., & Cech, T. R. (2014). A dimeric state for PRC2. Nucleic Acids Research, 42(14), 9236-9248. [gku540]. https://doi.org/10.1093/nar/gku540