Evidence for divergence of DNA methylation maintenance and a conserved inhibitory mechanism from DNA demethylation in chickens and mammals
| Autor: | Hiroshi Kimura, Mitsuo Oshimura, Yumi Asano, Miho Yoshii, Masako Tada, Ayaka Hayashi, Yoichi Matsuda, Takamasa Ito, Musashi Kubiura-Ichimaru |
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| Jazyk: | angličtina |
| Rok vydání: | 2021 |
| Předmět: |
0301 basic medicine
Methyltransferase Cellular differentiation Induced Pluripotent Stem Cells Biology Biochemistry Mammalian chromosome Dioxygenases Divergence 03 medical and health sciences chemistry.chemical_compound Mice 0302 clinical medicine Transcription (biology) Cell Line Tumor Genetics Animals Humans Epigenetics Molecular Biology DNA Modification Methylases Cells Cultured DNA methylation Mouse Embryonic Stem Cells Chicken Chromatin Cell biology DNA Demethylation 030104 developmental biology DNA demethylation chemistry Female Chickens 030217 neurology & neurosurgery DNA Research Article |
| Zdroj: | Genes & Genomics |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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