Meta-Biol

• Pathways

TET3 supplied by maternal cytoplasm is the major enzyme catalyzing oxidation of 5-methylcytidine to 5-hydroxymethylcytidine in the male pronucleus (inferred from mouse homologs in mouse zygotes). TET3-catalyzed demethylation is part of the second phase of active demethylation in the male pronucleus (inferred from mouse zygotes). The first phase appears to be catalyzed by cytidine deamination followed by base excision repair (inferred from mouse zygotes). Accumulation of 5-hydroxymethylcytidine requires the cytosine methylases DNMT3A and DNMT1 (inferred from mouse homologs in mouse zygotes). TET3 is present in both pronuclei of the zygote, however maternal 5-methylcytidine is protected from oxidation by DPPA3 (PGC7) bound to dimethyllysine-9 of histone H3 in maternal chromatin (inferred from mouse homologs in Nakamura et al. 2007, Nakamura et al. 2012). TET3 interacts with STGP4 (GSE), which interacts with METTL23 to localize TET3 to chromatin in pronuclei (inferred from mouse homologs in Hatanaka et al. 2017). TET1 and TET2 may also play a role in production of hydroxycytidine in the paternal genome (inferred from mouse embryos in Ficz et al. 2011).