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Structures of monomeric and dimeric PRC2:EZH1 reveal flexible modules involved in chromatin compaction

Cited 41 time in Web of Science Cited 40 time in Scopus
Authors

Grau, Daniel; Zhang, Yixiao; Lee, Chul-Hwan; Valencia-Sanchez, Marco; Zhang, Jenny; Wang, Miao; Holder, Marlene; Svetlov, Vladimir; Tan, Dongyan; Nudler, Evgeny; Reinberg, Danny; Walz, Thomas; Armache, Karim-Jean

Issue Date
2021-01
Publisher
Nature Publishing Group
Citation
Nature Communications, Vol.12 No.1, p. 714
Abstract
Polycomb repressive complex 2 (PRC2) is a histone methyltransferase critical for maintaining gene silencing during eukaryotic development. In mammals, PRC2 activity is regulated in part by the selective incorporation of one of two paralogs of the catalytic subunit, EZH1 or EZH2. Each of these enzymes has specialized biological functions that may be partially explained by differences in the multivalent interactions they mediate with chromatin. Here, we present two cryo-EM structures of PRC2:EZH1, one as a monomer and a second one as a dimer bound to a nucleosome. When bound to nucleosome substrate, the PRC2:EZH1 dimer undergoes a dramatic conformational change. We demonstrate that mutation of a divergent EZH1/2 loop abrogates the nucleosome-binding and methyltransferase activities of PRC2:EZH1. Finally, we show that PRC2:EZH1 dimers are more effective than monomers at promoting chromatin compaction, and the divergent EZH1/2 loop is essential for this function, thereby tying together the methyltransferase, nucleosome-binding, and chromatin-compaction activities of PRC2:EZH1. We speculate that the conformational flexibility and the ability to dimerize enable PRC2 to act on the varied chromatin substrates it encounters in the cell. Polycomb Repressive Complex 2 (PRC2) is a histone methyltransferase whose silencing activity is regulated in part by the selective incorporation of its catalytic subunits EZH1 or EZH2. Here, the authors capture an EZH1-containing PRC2 dimer on a nucleosome, demonstrating significant conformational changes during the process.
ISSN
2041-1723
URI
https://hdl.handle.net/10371/201838
DOI
https://doi.org/10.1038/s41467-020-20775-z
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  • College of Medicine
Research Area Epigenetics, Heterochromatin, Histone Modifications

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