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Front. Cell Dev. Biol. | doi: 10.3389/fcell.2018.00022

Tet enzymes, variants and differential effects on function

 Philippa Melamed1*, Yahav Yosefzon1,  Cfir David1, Anna Tsukerman1 and Lilach Pnueli1
  • 1Faculty of Biology, Technion – Israel Institute of Technology, Israel

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.

Keywords: TET enzymes, DNA Methylation, hydroxymethylation, isoforms, cxxc, Transcription, Genetic

Received: 26 Jan 2018; Accepted: 15 Feb 2018.

Edited by:

Alexey Ruzov, University of Nottingham, United Kingdom

Reviewed by:

Gerd P. Pfeifer, Van Andel Institute, United States
Yves Renaudineau, Université de Bretagne Occidentale, France  

Copyright: © 2018 Melamed, Yosefzon, David, Tsukerman and Pnueli. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.

* Correspondence: Prof. Philippa Melamed, Technion – Israel Institute of Technology, Faculty of Biology, Faculty of Biology, Technion-Israel Institute of Technology, Haifa, 32000, N/A, Israel, philippa.melamed@gmail.com