Abstract
5-methylcytosine (5mC) is the best understood DNA modification and is generally believed to be associated with repression of gene expression. Over the last decade, sequentially oxidized forms of 5mC (oxi-mCs) have been discovered within the genomes of vertebrates. Their discovery was accompanied by that of the ten-eleven translocation (TET) methylcytosine dioxygenases, the enzymes that catalyze the formation of the oxi-mCs. Although a number of studies performed on different vertebrate models and embryonic stem cells demonstrated that both TET enzymes and oxi-mCs are likely to be important for several developmental processes it is currently unclear whether their developmental roles are conserved among vertebrates. Here, we summarize recent developments in this field suggesting that biological roles of TETs/oxi-mCs may significantly differ between mice and zebrafish. Thus, although the role of TET proteins in late organogenesis has been documented for both these systems; unlike in mice the enzymatic oxidation of 5mC does not seem to be involved in zygotic reprogramming or gastrulation in zebrafish. Our analysis may provide an insight into the general principles of epigenetic regulation of animal development and cellular differentiation.
Highlights
Reviewed by: Yves Renaudineau, Université de Bretagne Occidentale, France Shicheng Guo, Marshfield Clinic Research Institute, Specialty section: This article was submitted to Epigenomics and Epigenetics, a section of the journal Frontiers in Cell and Developmental
The discovery that Thymine DNA glycosylase (TDG) can excise 5fC and 5caC, leaving an abasic site to be re-filled by non-modified cytosine, allowed a pathway for ten-eleven translocation (TET)-mediated active demethylation to be posited (He et al, 2011; Maiti and Drohat, 2011)
Cellular differentiation relies on the differential expression of thousands of genes
Summary
Reviewed by: Yves Renaudineau, Université de Bretagne Occidentale, France Shicheng Guo, Marshfield Clinic Research Institute, Specialty section: This article was submitted to Epigenomics and Epigenetics, a section of the journal Frontiers in Cell and Developmental. Over the past 8 years, renewed interest in active demethylation and the role of 5mC in development has been fueled by the discovery of a novel function for the ten-eleven translocation (TET) enzymes (Tahiliani et al, 2009; Ito et al, 2010) These enzymes catalyze the iterative oxidation of 5mC to: 5hydroxymethylcytosine (5hmC), 5-formylcytosine (5fC) and 5carboxylcytosine (5caC) (Kriaucionis and Heintz, 2009; Tahiliani et al, 2009; Ito et al, 2011), from here on collectively referred to as oxi-mCs. The discovery that Thymine DNA glycosylase (TDG) can excise 5fC and 5caC, leaving an abasic site to be re-filled by non-modified cytosine, allowed a pathway for TET-mediated active demethylation to be posited (He et al, 2011; Maiti and Drohat, 2011). A comprehensive discussion of currently proposed demethylation mechanisms is provided in the excellent review of Wu and Zhang (Wu and Zhang, 2017)
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