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Enhanced processivity of Dnmt1 by monoubiquitinated histone H3.
Genes to Cells ( IF 2.1 ) Pub Date : 2019-12-03 , DOI: 10.1111/gtc.12732
Yuichi Mishima 1 , Laura Brueckner 1 , Saori Takahashi 1 , Toru Kawakami 2 , Junji Otani 1 , Akira Shinohara 3 , Kohei Takeshita 4 , Ronald Garingalao Garvilles 1 , Mikio Watanabe 5 , Norio Sakai 5 , Hideyuki Takeshima 6 , Charlotte Nachtegael 1, 7 , Atsuya Nishiyama 8 , Makoto Nakanishi 8 , Kyohei Arita 9 , Kinichi Nakashima 10 , Hironobu Hojo 2 , Isao Suetake 1, 5, 11
Affiliation  

DNA methylation controls gene expression, and once established, DNA methylation patterns are faithfully copied during DNA replication by the maintenance DNA methyltransferase Dnmt1. In vivo, Dnmt1 interacts with Uhrf1, which recognizes hemimethylated CpGs. Recently, we reported that Uhrf1-catalyzed K18- and K23-ubiquitinated histone H3 binds to the N-terminal region (the replication focus targeting sequence, RFTS) of Dnmt1 to stimulate its methyltransferase activity. However, it is not yet fully understood how ubiquitinated histone H3 stimulates Dnmt1 activity. Here, we show that monoubiquitinated histone H3 stimulates Dnmt1 activity toward DNA with multiple hemimethylated CpGs but not toward DNA with only a single hemimethylated CpG, suggesting an influence of ubiquitination on the processivity of Dnmt1. The Dnmt1 activity stimulated by monoubiquitinated histone H3 was additively enhanced by the Uhrf1 SRA domain, which also binds to RFTS. Thus, Dnmt1 activity is regulated by catalysis (ubiquitination)-dependent and -independent functions of Uhrf1.

中文翻译:

单泛素化组蛋白H3增强Dnmt1的生产力。

DNA甲基化控制基因表达,一旦建立,DNA甲基化模式将在DNA复制过程中由维护DNA甲基转移酶Dnmt1忠实复制。在体内,Dnmt1与识别半甲基化CpGs的Uhrf1相互作用。最近,我们报道了Uhrf1催化的K18和K23泛素化的组蛋白H3与Dnmt1的N端区域(复制焦点靶向序列,RFTS)结合,以刺激其甲基转移酶活性。但是,尚未完全了解泛素化的组蛋白H3如何刺激Dnmt1活性。在这里,我们表明,单泛素化的组蛋白H3刺激Dnmt1对具有多个半甲基化CpG的DNA的活性,而不是对仅具有一个半甲基化CpG的DNA的活性,表明泛素化对Dnmt1的合成能力有影响。单泛素化的组蛋白H3刺激的Dnmt1活性通过Uhrf1 SRA域(与RFTS结合)可加性增强。因此,Dnmt1活性受Uhrf1的催化(泛素化)依赖性和非依赖性功能调节。
更新日期:2019-11-01
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