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KMID : 0381120210430030269
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Genes and Genomics
2021 Volume.43 No. 3 p.269 ~ p.280
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Evidence for divergence of DNA methylation maintenance and a conserved inhibitory mechanism from DNA demethylation in chickens and mammals
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Tada Masako
Hayashi Ayaka
Asano Yumi
Kubiura-Ichimaru Musashi
Ito Takamasa
Yoshii Miho
Kimura Hiroshi
Matsuda Yoichi
Oshimura Mitsuo
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Abstract
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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.
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KEYWORD
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DNA methylation, Chicken, Mammalian chromosome, Divergence
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