Mrg15 stimulates Ash1 H3K36 methyltransferase activity and facilitates Ash1 Trithorax group protein function in Drosophila.

Mrg15 stimulates Ash1 H3K36 methyltransferase activity and facilitates Ash1 Trithorax group protein function in Drosophila.
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Mrg15 刺激果蝇中 Ash1 H3K36 甲基转移酶活性并促进 Ash1 Trithorax 组蛋白功能。

DOI:
10.1038/s41467-017-01897-3
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发表时间:
2017-11-21
影响因子:
16.6
通讯作者:
Zhu B
Zhu B
中科院分区:
综合性期刊1区
文献类型:
--
作者:
Huang C;Yang F;Zhang Z;Zhang J;Cai G;Li L;Zheng Y;Chen S;Xi R;Zhu B

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Ash 1是一种三胸组蛋白,具有H3 K36特异性组蛋白甲基转移酶活性,可拮抗Polycomb沉默。在这里,我们报告的两个阿什1复合物亚基,Mrg 15和Nurf 55的鉴定。在体外,Mrg 15刺激Ash 1的酶活性。在体内,Mrg 15被Ash 1募集到它们的共同靶标,并且Mrg 15加强Ash 1染色质缔合并促进H3 K36 me 2的适当沉积。为了剖析Mrg 15在Ash 1复合物中的功能作用,我们鉴定了一个Ash 1点突变(Ash 1-R1288 A),该突变显示出与Mrg 15的相互作用大大减弱。携带该突变的敲入果蝇显示出多种同源异型转化表型,并且这些表型通过过表达Mrg 15-Nurf 55融合蛋白而被部分拯救,该融合蛋白稳定了Mrg 15与Ash 1的结合。总之,Mrg 15是一个亚基的阿什1复合物,刺激剂的阿什1酶活性和一个关键的调节器的TrxG蛋白功能的阿什1在果蝇。Ash 1是一种H3 K36甲基转移酶,三胸组蛋白,在拮抗Polycomb沉默中至关重要。在这里,作者纯化了果蝇Ash 1复合体,并将Mrg 15和Nurf 55鉴定为亚基,发现Mrg 15被Ash 1招募并增强了Ash 1的活性。
Ash1 is a Trithorax group protein that possesses H3K36-specific histone methyltransferase activity, which antagonizes Polycomb silencing. Here we report the identification of two Ash1 complex subunits, Mrg15 and Nurf55. In vitro, Mrg15 stimulates the enzymatic activity of Ash1. In vivo, Mrg15 is recruited by Ash1 to their common targets, and Mrg15 reinforces Ash1 chromatin association and facilitates the proper deposition of H3K36me2. To dissect the functional role of Mrg15 in the context of the Ash1 complex, we identify an Ash1 point mutation (Ash1-R1288A) that displays a greatly attenuated interaction with Mrg15. Knock-in flies bearing this mutation display multiple homeotic transformation phenotypes, and these phenotypes are partially rescued by overexpressing the Mrg15-Nurf55 fusion protein, which stabilizes the association of Mrg15 with Ash1. In summary, Mrg15 is a subunit of the Ash1 complex, a stimulator of Ash1 enzymatic activity and a critical regulator of the TrxG protein function of Ash1 in Drosophila. Ash1 is an H3K36 methyltransferase, Trithorax group protein and is critical in antagonizing Polycomb silencing. Here, the authors purify the Drosophila Ash1 complex and identify Mrg15 and Nurf55 as subunits, finding that Mrg15 is recruited by Ash1 and reinforces Ash1 activity.
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发表时间: 2016-04-28
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