H3K14ac is linked to methylation of H3K9 by the triple Tudor domain of SETDB1.
H3K14ac is linked to methylation of H3K9 by the triple Tudor domain of SETDB1.
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H3K14ac 通过 SETDB1 的三重 Tudor 结构域与 H3K9 甲基化相关
DOI：
10.1038/s41467-017-02259-9
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发表时间：
2017-12-12
影响因子：
16.6
通讯作者：
Jeltsch A
中科院分区：
文献类型：
--
作者：
Jurkowska RZ;Qin S;Kungulovski G;Tempel W;Liu Y;Bashtrykov P;Stiefelmaier J;Jurkowski TP;Kudithipudi S;Weirich S;Tamas R;Wu H;Dombrovski L;Loppnau P;Reinhardt R;Min J;Jeltsch A
SETDB1是一种重要的H3K9甲基转移酶，参与了逆转录病毒的沉默和基因调控。我们发现它的三个Tudor结构域(3TD)与含有K14乙酰化和K9甲基化的双重修饰的组蛋白H3特异性结合。3TD与H3K14ac/K9Me多肽的晶体结构表明，多肽结合和K14ac识别发生在Tudor结构域(TD)TD2和TD3的界面上。结构和生化数据证明了组蛋白密码阅读过程中的口袋开关机制，因为K9me1或K9me2优先被TD3的芳香笼子识别，而K9me3选择性地与TD2结合。K14ac/K9me结合位点的突变改变了3TD的亚核定位。芯片序列分析表明，SETDB1在H3K9me3区域富含SETDB1，K9me3/K14ac在与LINE元件重叠的SETDB1结合部位富含，这表明SETDB1复合体在K14ac/K9me区域的募集在基因组活性区域的沉默中起到了作用。
SETDB1 is an essential H3K9 methyltransferase involved in silencing of retroviruses and gene regulation. We show here that its triple Tudor domain (3TD) specifically binds to doubly modified histone H3 containing K14 acetylation and K9 methylation. Crystal structures of 3TD in complex with H3K14ac/K9me peptides reveal that peptide binding and K14ac recognition occurs at the interface between Tudor domains (TD) TD2 and TD3. Structural and biochemical data demonstrate a pocket switch mechanism in histone code reading, because K9me1 or K9me2 is preferentially recognized by the aromatic cage of TD3, while K9me3 selectively binds to TD2. Mutations in the K14ac/K9me binding sites change the sub-nuclear localization of 3TD. ChIP-seq analyses show that SETDB1 is enriched at H3K9me3 regions and K9me3/K14ac is enriched at SETDB1 binding sites overlapping with LINE elements, suggesting that recruitment of the SETDB1 complex to K14ac/K9me regions has a role in silencing of active genomic regions.
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DOI：
10.1016/j.tig.2015.11.001
发表时间：
2016-01
期刊：
Trends in genetics : TIG
影响因子：
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作者：
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