Melamed Philippa, Yosefzon Yahav, David Cfir, Tsukerman Anna, Pnueli Lilach
Faculty of Biology, Technion-Israel Institute of Technology, Haifa, Israel.
Front Cell Dev Biol. 2018 Mar 5;6:22. doi: 10.3389/fcell.2018.00022. eCollection 2018.
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 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.
大约10年前，10-11易位1（TET）甲基胞嘧啶双加氧酶家族的发现，预示着在理解DNA表观遗传修饰方面取得了重大突破。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DNA主动去甲基化的其他反应。尽管这些酶在分化组织中也广泛表达，但在胚胎干细胞中已经广泛研究了TET酶以及5hmC与基因组活性调控区域的关联。然而，由于在不同组织中利用了不同的调控区域，TET1和TET3以多种异构体形式存在。其中一些异构体，如TET2，缺乏CXXC结构域，这可能对它们在基因组中募集到特定区域有重大影响，而在某些情况下，TET1却反常地抑制转录。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以及对其活性可能产生的影响。
