Tet1 is well known initiatior of DNA demethylation by converting 5-methylcytosine to 5-hydroxymethylcytosine in CpG-rich regions of the brain. There have been studies using Tet1-KO mice about adult neurogenesis, cognition and memory extinction, it is still unclear whether Tet1 overexpression is beneficial for CNS networks. Thus in this study, Tet1 overexpression TG mice were developed and behavioral phenotypes were analyzed with related gene studies. Most of all, they showed anxiety-like behaviors and improved memories with increased immature neurons in the hippocampal dentate gyrus. Hence, they showed increased immediate-early gene levels (c-Fos, Arc, Egr-1, and BDNF), activation of intracellular calcium signaling (CamKII, ERK, and CREB) and changes in the expression of GABA receptor subunits (GABRA2, and GABRA4) in several brain regions. By overexpressing Tet1 in NB41A3 cells, effect of Tet1 overexpression on intracellular calcium levels with higher Egr-1 promoter activity was evaluated. These findings suggests Tet1 overexpression affects excitatory synaptic networks via activating NMDAR-dependent calcium signaling which leads to dysregulation of inhibitory synaptic networks. Also, it implies chronic and excessive activation of intraneuronal calcium signaling by Tet1 leads to behavioral differences in mice. Additionally, it suggests Tet1 overexpression in the PFC, hippocampus, and amygdala contributes as both beneficial and harmful for neural networks in differing aspects.

Epigenetic regulations including DNA methylation, long noncoding RNAs and histone modification are considered to be involved in many biological processes. Such regulations in general begin with change of covalent bonds on the substrates. Moieties involving the covalent bond include methyl- and acetyl-group, glucose, SUMO and etc. Among them, methyl group-mediated modulation is commonly observed in all three substrates. Mouse primordial germ cells (PGCs) first appear at embryonic day (E)7.25 on the base of the allantois, and then migrate through the hindgut to the genital ridge. Once PGCs reach genital ridge, they become dimorphic, in that female PGCs undergo meiosis whereas male PGCs are mitotically arrested. Meiosis is a germ-cell-specific cell division process through which haploid gametes are produced for sexual reproduction. Before the initiation of meiosis, mouse primordial germ cells undergo a series of epigenetic reprogramming steps including the global erasure of DNA methylation at the 5-position of cytosine (5mC) in CpG-rich DNA. I will discuss role of Ten-to-Eleven translocation (Tet) in DNA demethylation in the process of PGC reprogramming.