National Institutes of Health/National Institute of General Medical Sciences (NIH/NIGMS)
R01 GM115882
米国
引用
ジャーナル: Nat Commun / 年: 2021 タイトル: Structures of monomeric and dimeric PRC2:EZH1 reveal flexible modules involved in chromatin compaction. 著者: Daniel Grau / Yixiao Zhang / Chul-Hwan Lee / Marco Valencia-Sánchez / Jenny Zhang / Miao Wang / Marlene Holder / Vladimir Svetlov / Dongyan Tan / Evgeny Nudler / Danny Reinberg / Thomas Walz ...著者: Daniel Grau / Yixiao Zhang / Chul-Hwan Lee / Marco Valencia-Sánchez / Jenny Zhang / Miao Wang / Marlene Holder / Vladimir Svetlov / Dongyan Tan / Evgeny Nudler / Danny Reinberg / Thomas Walz / Karim-Jean Armache / 要旨: 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 ...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.
フィルム・検出器のモデル: GATAN K3 (6k x 4k) / 平均電子線量: 56.7 e/Å2
電子線
加速電圧: 300 kV / 電子線源: FIELD EMISSION GUN
電子光学系
照射モード: SPOT SCAN / 撮影モード: BRIGHT FIELD
実験機器
モデル: Titan Krios / 画像提供: FEI Company
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画像解析
粒子像選択
選択した数: 3410000 / 詳細: Template based picking
CTF補正
ソフトウェア - 名称: cryoSPARC / 詳細: Patch CTF correction
最終 再構成
解像度のタイプ: BY AUTHOR / 解像度: 4.8 Å / 解像度の算出法: FSC 0.143 CUT-OFF 詳細: Values provided are for the PRC2B map portion of the 3-component composite map. Other parts of the composite map used: nucleosome: 56616 particles, 3.3 angstroms. PRC2A: 18151 particles, 4.1 angstroms. 使用した粒子像数: 26440