Evolutionary adaptation of the fly Pygo PHD finger toward recognizing histone H3 tail methylated at arginine 2.
Evolutionary adaptation of the fly Pygo PHD finger toward recognizing histone H3 tail methylated at arginine 2.
复制标题
DOI：
10.1016/j.str.2013.09.013
复制
发表时间：
2013-12-03
期刊：
影响因子：
5.7
通讯作者：
Bienz, Mariann
中科院分区：
文献类型：
--
作者：
Miller, Thomas C. R.;Mieszczanek, Juliusz;Jose Sanchez-Barrena, Maria;Rutherford, Trevor J.;Fiedler, Marc;Bienz, Mariann
Pygo蛋白通过解除Wnt靶点的Groucho依赖性抑制来促进Armadillo和β-catenin依赖性转录。它们的PHD指结合在赖氨酸4处甲基化的组蛋白H3尾，并结合它们的Legless/BCL 9辅因子的HD 1结构域，将Pygo连接到Armadillo/β-catenin。有趣的是，蝇Pygo直系同源物在其组蛋白口袋分隔物中表现出色氨酸>苯丙氨酸取代，这降低了它们对组蛋白的亲和力。在这里，我们使用X射线晶体学和NMR，发现一个明显的沟接壤的果蝇PHD-HD 1复杂的苯丙氨酸-半芳香族笼识别不对称甲基化精氨酸2（R2 me 2a），染色质标记沉默的基因。我们的三元复合物的结构模型揭示了一个独特的模式，二甲基精氨酸识别，涉及R2 me 2a和它的沟，其结构的完整性是至关重要的正常组织图案之间的极性相互作用。值得注意的是，人源化的苍蝇Pygo去抑制Notch靶标，这意味着经典Pygo直系同源物的固有Notch相关功能在苍蝇Pygo中被禁用，因此似乎专用于Wnt信号传导。果蝇Pygo PHD指中的共适应突变改变了它们的组蛋白结合表面。果蝇Pygo中的半芳香族沟嵌入组蛋白H3的二甲基化精氨酸2。精氨酸2沟的结构完整性是组织图案化所必需的。表明果蝇Pygo PHD指中的共适应突变改变了其组蛋白结合表面，使其包含一个新的半芳香族凹槽，该凹槽嵌入组蛋白H3尾部的不对称甲基化精氨酸2，这是沉默基因的染色质标记。
Pygo proteins promote Armadillo- and β-catenin-dependent transcription, by relieving Groucho-dependent repression of Wnt targets. Their PHD fingers bind histone H3 tail methylated at lysine 4, and to the HD1 domain of their Legless/BCL9 cofactors, linking Pygo to Armadillo/β-catenin. Intriguingly, fly Pygo orthologs exhibit a tryptophan > phenylalanine substitution in their histone pocket-divider which reduces their affinity for histones. Here, we use X-ray crystallography and NMR, to discover a conspicuous groove bordering this phenylalanine in the Drosophila PHD-HD1 complex—a semi-aromatic cage recognizing asymmetrically methylated arginine 2 (R2me2a), a chromatin mark of silenced genes. Our structural model of the ternary complex reveals a distinct mode of dimethylarginine recognition, involving a polar interaction between R2me2a and its groove, the structural integrity of which is crucial for normal tissue patterning. Notably, humanized fly Pygo derepresses Notch targets, implying an inherent Notch-related function of classical Pygo orthologs, disabled in fly Pygo, which thus appears dedicated to Wnt signaling. Coadapted mutations in fly Pygo PHD fingers alter their histone-binding surface A semi-aromatic groove in fly Pygo embeds dimethylated arginine 2 of histone H3 Structural integrity of the arginine 2 groove is required for tissue patterning Humanized Drosophila Pygo derepresses Notch targets Miller et al. show that coadapted mutations in the Drosophila Pygo PHD finger alter its histone-binding surface to contain a novel semi-aromatic groove that embeds asymmetrically methylated arginine 2 of the histone H3 tail, a chromatin mark of silenced genes.
登录
查看更多内容
影响因子：
64.5
作者：
Kramps, T;Peter, O;Basler, K
通讯作者：
Basler, K
影响因子：
10.5
作者：
Brembeck, FH;Schwarz-Romond, T;Birchmeier, W
通讯作者：
Birchmeier, W
影响因子：
9.2
作者：
de la Roche, Marc;Bienz, Mariann
通讯作者：
Bienz, Mariann
影响因子：
56.9
作者：
Huang, Y;Fang, J;Xu, RM
通讯作者：
Xu, RM
Pygo2 通过促进组蛋白 H3 K4 甲基化来扩增乳腺祖细胞
DOI：
10.1083/jcb.200810133
发表时间：
2009-06-01
期刊：
The Journal of cell biology
影响因子：
--
作者：
Gu B;Sun P;Yuan Y;Moraes RC;Li A;Teng A;Agrawal A;Rhéaume C;Bilanchone V;Veltmaat JM;Takemaru K;Millar S;Lee EY;Lewis MT;Li B;Dai X
通讯作者：
Dai X