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Evidence for divergence of DNA methylation maintenance and a conserved inhibitory mechanism from DNA demethylation in chickens and mammals

Genes & Genomics 2021년 43권 3호 p.269 ~ 280
Tada Masako, Hayashi Ayaka, Asano Yumi, Kubiura-Ichimaru Musashi, Ito Takamasa, Yoshii Miho, Kimura Hiroshi, Matsuda Yoichi, Oshimura Mitsuo,
소속 상세정보
 ( Tada Masako ) - Toho University Faculty of Science Department of Biology
 ( Hayashi Ayaka ) - Tottori University Chromosome Engineering Research Center
 ( Asano Yumi ) - Tottori University Chromosome Engineering Research Center
 ( Kubiura-Ichimaru Musashi ) - Toho University Faculty of Science Department of Biology
 ( Ito Takamasa ) - Toho University Faculty of Science Department of Biology
 ( Yoshii Miho ) - Toho University Faculty of Science Department of Biology
 ( Kimura Hiroshi ) - Tokyo Institute of Technology Institute of Innovative Research Cell Biology Unit
 ( Matsuda Yoichi ) - Nagoya University Graduate School of Bioagricultural Sciences Department of Animal Sciences
 ( Oshimura Mitsuo ) - Tottori University Chromosome Engineering Research Center

Abstract


Background: DNA methylation is a significant epigenetic modification 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 differently regulated in diverged species.

Methods: Chicken B-cell lymphoma DT40 cells were used as an avian model to compare differences in the overall regulation of DNA modification 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 differences 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 different target sequence recognition systems, suggesting that factors inducing DNMT?DNA association have already diverged.

키워드

DNA methylation; Chicken; Mammalian chromosome; Divergence

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