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Review
. 2020 Nov;15(11):1139-1150.
doi: 10.1080/15592294.2020.1767323. Epub 2020 May 18.

Ten-eleven translocation proteins and their role beyond DNA demethylation - what we can learn from the fly

Joy N Ismail  1   2 , Mirna Ghannam  1   2 , Amani Al Outa  3 , Felice Frey  1   2 , Margret Shirinian  1   2
Affiliations
Review

Ten-eleven translocation proteins and their role beyond DNA demethylation - what we can learn from the fly

Joy N Ismail et al. Epigenetics. 2020 Nov.

Abstract

Ten-eleven Translocation (TET) proteins have emerged as a family of epigenetic regulators that are important during development and have been implicated in various types of cancers. TET is a highly conserved protein that has orthologues in almost all multicellular organisms. Here, we review recent literature on the novel substrate specificity of this family of DNA 5-methylcytosine demethylases on DNA 6-methyladenine and RNA 5-methylcytosine that were first identified in the invertebrate model Drosophila. We focus on the biological role of these novel epigenetic marks in the fruit fly and mammals and highlight TET proteins' critical function during development specifically in brain development.

Keywords: DNA demethylation; Drosophila; cancer biology; epigenetics; neuroscience.

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Conflict of interest statement

No potential conflict of interest was reported by the authors.

Figures

Figure 1.
Figure 1.
TET-driven demethylation on different substrates (RNA/DNA) in mammals and D. melanogaster. (a) TET in mammals and D. melanogaster demethylates the DNA on cytosines and adenosines, respectively. RNA demethylation is also carried out by TET in D. melanogaster; however, it has only been investigated in vitro in mammals. (b) A schematic representation of active DNA demethylation by TET, TDG (thymidine-DNA-glycosylase) and BER (base excision repair)-mediated pathways
Figure 2.
Figure 2.
Comparison of human and D. melanogaster TET protein structure and expression. (a). Three TET proteins are found in humans in comparison to one TET (dTet) homologue in D. melanogaster. All share a conserved cysteine-rich domain (dark blue colour) and a DSBH (Double Stranded Beta-Helix) domain (dark grey colour). TET2 lacks the CXXC DNA binding domain (light blue colour). The Fe(II)-binding site (red colour) and 2-oxoglutarate binding site (yellow colour) are both located within the catalytic domain. (b). An overview of TET expressing tissues in humans and D. melanogaster.
Figure 3.
Figure 3.
Comparison between the function of TET proteins in D. melanogaster and mammals
See this image and copyright information in PMC

References

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