Chromosomal distribution patterns of global 5mC and 5hmC on the ZZ/ZW and XX/XY chromosomes in the Japanese wrinkled frog, Rana rugosa, induced by Tet methylcytosine dioxygenase enzymes

Tet methylcytosine dioxygenase enzymes catalyze the conversion of DNA methylcytosine (5mC) to 5-hydroxymethylcytosine (5hmC), thereby initiating DNA demethylation. In mice, Tets also regulate gene activity by binding the regulatory elements of target genes. 5hmC is associated with euchromatic regions and epigenetic reprogramming events. In this study, we examined the levels of 5mC and 5hmC in two major groups of Japanese wrinkled frogs (Rana rugosa) with morphologically distinct sex chromosome constitutions, ZZ/ZW and XX/ XY. Patterns of 5mC and 5hmC, as determined by immunostaining, were indistinguishable between homologous sex chromosomes in ZZ cells and XX cells. Genome-wide conversion of 5mC to 5hmC, followed by cell cycle-mediated dilution, was induced in PHA-stimulated peripheral blood cells in adult frogs. Tet enzymes may share an evolutionarily conserved function associated with a global epigenetic reprogramming event during dedifferentiation in mammals and frogs.