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

Figures & data

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

Table 1. The function of 6mA and 5hmrC modification in different multicellular organisms

Modification	Multicellular organism	Function	Correlation with gene expression	Reference
6mA	A. thaliana	protein coding gene regulation	activation	Liang et al. 2018
	B. mori	regulates cell cycle progression	repression	Wang et al. 2018
	C. elegans	gene regulation, regulation of stress response, transgenerational inheritance	activation	Greer et al. 2015 Ma et al. 2019
	D. melanogaster	regulates transposon expression in ovary regulates neuronal gene expression in brains regulates transcription in whole fly	activation repression repression	Zhang et al. 2015 Yao et al. 2018 Shah et al. 2019
	D. rerio and S. scrofa	involved in embryogenesis, activation of repetitive elements	activation	Liu et al. 2016
	H. sapiens	prevents tumorigenesis	activation	Xiao et al. 2018
	M. musculus	regulates expression of neuronal genes and LINE transposon expression in stress condition	repression	Yao et al. 2017
	O. sativa	gene regulation, repression of transposable element-related genes	gene-dependent	Zhou et al. 2018
	T. thermophile	contributes to nucleosome positioning	gene-dependent	Wang et al. 2017
	X. laevis	regulates transcription, nucleic acid binding, metabolic processes, cell adhesion and ATP binding activity	N/A	Koziol et al. 2016
5hmrC	D. melanogaster	regulates embryogenesis/development	gene-dependent	Delatte et al. 2016
	M. musculus	decrease detected in model of Parkinson’s disease	N/A	Miao et al. 2016
	M. musculus and H. sapiens	regulates gene expression	N/A	Fu et al. 2014

Abbreviations

5mC: 5-methylcytosine

5hmC: 5-hydroxylmethylcytosine

TET: Ten-eleven Translocation

DNMT: DNA methyltransferase

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. Comparison between the function of TET proteins in D. melanogaster and mammals