A D53 repression motif induces oligomerization of TOPLESS corepressors and promotes assembly of a corepressor-nucleosome complex.
A D53 repression motif induces oligomerization of TOPLESS corepressors and promotes assembly of a corepressor-nucleosome complex.
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DOI：
10.1126/sciadv.1601217
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发表时间：
2017-06
期刊：
影响因子：
13.6
通讯作者：
Melcher K
中科院分区：
文献类型：
--
作者：
Ma H;Duan J;Ke J;He Y;Gu X;Xu TH;Yu H;Wang Y;Brunzelle JS;Jiang Y;Rothbart SB;Xu HE;Li J;Melcher K
水稻D53抑制基序连接TPL辅阻遏子的两个位点，介导TPL寡聚和核小体结合。无上胸是保守的Tup1/Groucho/TLE(Split的转导素样增强子)家族的四聚体植物辅阻遏子。我们发现它们通过它们的无上部域(TPD)与水稻三叉内酯信号抑制因子D53的两个功能重要的乙烯反应因子相关的两亲性抑制(EAR)基序相互作用：普遍保守的EAR-3和单子叶特异的EAR-2。我们报道了单子叶特异的EAR-2多肽与无顶相关蛋白2(TPR2)TPD的复合体的晶体结构，其中EAR-2基序与茉莉酸和生长素信号抑制物结合在同一TPD槽上，但与第二个TPD位点额外接触，介导TPD四聚体-四聚体相互作用。我们在报告基因检测和转基因水稻中验证了这两个TPD结合位点的功能相关性，并证明了EAR-2结合诱导了TPD寡聚。此外，我们证明TPD直接结合核小体和组蛋白H3和H4的尾巴。EAR-2结合诱导的TPD复合体的高阶组装显著稳定了核小体-TPD相互作用。这些结果建立了一种新的TPD-抑制子结合模式，促进了TPD齐聚和TPD-核小体相互作用，从而说明了抑制子-辅阻遏子-核小体复合体的初始组装。
Rice D53 repression motif links two sites of TPL corepressors to mediate TPL oligomerization and nucleosome association. TOPLESS are tetrameric plant corepressors of the conserved Tup1/Groucho/TLE (transducin-like enhancer of split) family. We show that they interact through their TOPLESS domains (TPDs) with two functionally important ethylene response factor–associated amphiphilic repression (EAR) motifs of the rice strigolactone signaling repressor D53: the universally conserved EAR-3 and the monocot-specific EAR-2. We present the crystal structure of the monocot-specific EAR-2 peptide in complex with the TOPLESS-related protein 2 (TPR2) TPD, in which the EAR-2 motif binds the same TPD groove as jasmonate and auxin signaling repressors but makes additional contacts with a second TPD site to mediate TPD tetramer-tetramer interaction. We validated the functional relevance of the two TPD binding sites in reporter gene assays and in transgenic rice and demonstrate that EAR-2 binding induces TPD oligomerization. Moreover, we demonstrate that the TPD directly binds nucleosomes and the tails of histones H3 and H4. Higher-order assembly of TPD complexes induced by EAR-2 binding markedly stabilizes the nucleosome-TPD interaction. These results establish a new TPD-repressor binding mode that promotes TPD oligomerization and TPD-nucleosome interaction, thus illustrating the initial assembly of a repressor-corepressor-nucleosome complex.