Tet Enzymes, Variants, and Differential Effects on Function.
Tet Enzymes, Variants, and Differential Effects on Function.
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DOI：
10.3389/fcell.2018.00022
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发表时间：
2018
影响因子：
5.5
通讯作者：
Pnueli L
中科院分区：
文献类型：
--
作者：
Melamed P;Yosefzon Y;David C;Tsukerman A;Pnueli L
近10年前，10 - 11易位1 （TET）甲基胞嘧啶双加氧酶家族的发现预示着对DNA表观遗传修饰的理解取得了重大突破。最初被描述为催化甲基胞嘧啶（5mC）氧化为羟甲基胞嘧啶（5hmC），现在很清楚，这些酶还可以催化导致活性DNA去甲基化的其他反应。TET酶和5hmC与基因组活性调控区域的关联已经在胚胎干细胞中得到了广泛的研究，尽管这些酶在分化组织中也广泛表达。然而，由于在不同的组织中利用了替代的调控区域，TET1和TET3被发现为不同的同种异构体。其中一些同工型，如TET2，缺乏CXXC结构域，这可能对它们在基因组中特定位点的募集有重要影响，而在某些情况下，TET1被视为抑制转录的矛盾之处。在这篇综述中，我们汇集了这些Tet异构体差异调控的新方面及其活性的可能后果。
Discovery of the ten-eleven translocation 1 (TET) methylcytosine dioxygenase family of enzymes, nearly 10 years ago, heralded a major breakthrough in understanding the epigenetic modifications of DNA. Initially described as catalyzing the oxidation of methyl cytosine (5mC) to hydroxymethyl cytosine (5hmC), it is now clear that these enzymes can also catalyze additional reactions leading to active DNA demethylation. The association of TET enzymes, as well as the 5hmC, with active regulatory regions of the genome has been studied extensively in embryonic stem cells, although these enzymes are expressed widely also in differentiated tissues. However, TET1 and TET3 are found as various isoforms, as a result of utilizing alternative regulatory regions in distinct tissues. Some of these isoforms, like TET2, lack the CXXC domain which probably has major implications on their recruitment to specific loci in the genome, while in certain contexts TET1 is seen paradoxically to repress transcription. In this review we bring together these novel aspects of the differential regulation of these Tet isoforms and the likely consequences on their activity.