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      저자 : Mitsuo Oshimura (검색결과 1 건)
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        Evidence for divergence of DNA methylation maintenance and a conserved inhibitory mechanism from DNA demethylation in chickens and mammals

        Masako Tada,Ayaka Hayashi,Yumi Asano,Musashi Kubiura-Ichimaru,Takamasa Ito,Miho Yoshii,Hiroshi Kimura,Yoichi Matsuda,Mitsuo Oshimura 한국유전학회 2021 Genes & Genomics Vol.43 No.3

        Background DNA methylation is a signifcant epigenetic modifcation that is evolutionarily conserved in various species and often serves as a repressive mark for transcription. DNA methylation levels and patterns are regulated by a balance of opposing enzyme functions, DNA methyltransferases, DNMT1/3A/3B and methylcytosine dioxygenases, TET1/2/3. In mice, the TET enzyme converts DNA cytosine methylation (5mC) to 5-hydroxymethylcytosine (5hmC) at the beginning of fertilisation and gastrulation and initiates a global loss of 5mC, while the 5mC level is increased on the onset of cell differentiation during early embryonic development. Objective Global loss and gain of DNA methylation may be diferently regulated in diverged species. Methods Chicken B-cell lymphoma DT40 cells were used as an avian model to compare diferences in the overall regulation of DNA modifcation with mammals. Results We found that DNA methylation is maintained at high levels in DT40 cells through compact chromatin formation, which inhibits TET-mediated demethylation. Human and mouse chromosomes introduced into DT40 cells by cell fusion lost the majority of 5mC, except for human subtelomeric repeats. Conclusion Our attempt to elucidate the diferences in the epigenetic regulatory mechanisms between birds and mammals explored the evidence that they share a common chromatin-based regulation of TET–DNA access, while chicken DNMT1 is involved in diferent target sequence recognition systems, suggesting that factors inducing DNMT–DNA association have already diverged.

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