Format

Send to

Choose Destination
Nucleic Acids Res. 2014 Aug;42(14):9236-48. doi: 10.1093/nar/gku540. Epub 2014 Jul 3.

A dimeric state for PRC2.

Author information

1
Department of Chemistry & Biochemistry, Howard Hughes Medical Institute, University of Colorado BioFrontiers Institute, Boulder, CO 80309-0596, USA.
2
Department of Chemistry & Biochemistry, Howard Hughes Medical Institute, University of Colorado BioFrontiers Institute, Boulder, CO 80309-0596, USA thomas.cech@colorado.edu.

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.

PMID:
24992961
PMCID:
PMC4132707
DOI:
10.1093/nar/gku540
[Indexed for MEDLINE]
Free PMC Article

Supplemental Content

Full text links

Icon for Silverchair Information Systems Icon for PubMed Central
Loading ...
Support Center