Interactions within the mammalian DNA methyltransferase family.
Interactions within the mammalian DNA methyltransferase family.
复制标题
哺乳动物DNA甲基转移酶家族中的相互作用。
DOI：
10.1186/1471-2199-4-7
复制
发表时间：
2003-05-30
影响因子：
--
通讯作者：
Leonhardt H
中科院分区：
文献类型：
--
作者：
Margot JB;Ehrenhofer-Murray AE;Leonhardt H
在哺乳动物中，表观遗传信息是通过DNA甲基转移酶Dnmt 1、Dnmt 3a和Dnmt 3b对胞嘧啶残基的复制后甲基化来建立和维持的。Dnmt 1是维持甲基化所必需的，而Dnmt 3a和Dnmt 3b负责从头甲基化。与Dnmt 3a或Dnmt 3b相反，Dnmt 1的分离的C-末端区域是无催化活性的，尽管存在活性DNA甲基转移酶的典型序列基序。缺失分析表明，大部分的N-末端结构域是酶活性所需的。利用酵母双杂交系统研究了N端结构域在这一调控中所起的作用。我们在这里展示了Dnmt 1中存在分子内相互作用，但Dnmt 3a或Dnmt 3b中没有。这种相互作用被证实免疫沉淀，并通过缺失定位。此外，对Dnmt家族成员之间相互作用的系统分析表明，DNMT 3L与Dnmt 3a和Dnmt 3b的C-末端结构域相互作用。Dnmt 1的分离的C-末端结构域的甲基化能力的缺乏可以部分地由N-和C-末端结构域之间的物理相互作用来解释，所述物理相互作用显然是催化结构域的活化所需的。我们的缺失分析表明，Dnmt 1的三级结构是重要的，而不是一个特定的序列基序在这个过程中。此外，DNMT 3L与Dnmt 3a和Dnmt 3b的C-末端结构域之间的相互作用表明了一种机制，即无酶活性的DNMT 3L通过募集活性甲基化酶来引起其底物的甲基化。
In mammals, epigenetic information is established and maintained via the postreplicative methylation of cytosine residues by the DNA methyltransferases Dnmt1, Dnmt3a and Dnmt3b. Dnmt1 is required for maintenance methylation whereas Dnmt3a and Dnmt3b are responsible for de novo methylation. Contrary to Dnmt3a or Dnmt3b, the isolated C-terminal region of Dnmt1 is catalytically inactive, despite the presence of the sequence motifs typical of active DNA methyltransferases. Deletion analysis has revealed that a large part of the N-terminal domain is required for enzymatic activity. The role played by the N-terminal domain in this regulation has been investigated using the yeast two-hybrid system. We show here the presence of an intra-molecular interaction in Dnmt1 but not in Dnmt3a or Dnmt3b. This interaction was confirmed by immunoprecipitation and was localized by deletion mapping. Furthermore, a systematic analysis of interactions among the Dnmt family members has revealed that DNMT3L interacts with the C-terminal domain of Dnmt3a and Dnmt3b. The lack of methylating ability of the isolated C-terminal domain of Dnmt1 could be explained in part by a physical interaction between N- and C-terminal domains that apparently is required for activation of the catalytic domain. Our deletion analysis suggests that the tertiary structure of Dnmt1 is important in this process rather than a particular sequence motif. Furthermore, the interaction between DNMT3L and the C-terminal domains of Dnmt3a and Dnmt3b suggests a mechanism whereby the enzymatically inactive DNMT3L brings about the methylation of its substrate by recruiting an active methylase.
登录
查看更多内容
影响因子：
10.5
作者：
Hendrich, B;Guy, J;Bird, A
通讯作者：
Bird, A
影响因子：
4.8
作者：
Gowher, H;Jeltsch, A
通讯作者：
Jeltsch, A
影响因子：
14.9
作者：
Deplus, R;Brenner, C;Fuks, F
通讯作者：
Fuks, F
影响因子：
2.9
作者：
Flynn, J;Glickman, JF;Reich, NO
通讯作者：
Reich, NO
影响因子：
14.9
作者：
Liu, YL;Oakeley, EJ;Jost, JP
通讯作者：
Jost, JP