RRC ID 71564
Author Tada M, Hayashi A, Asano Y, Kubiura-Ichimaru M, Ito T, Yoshii M, Kimura H, Matsuda Y, Oshimura M.
Title Evidence for divergence of DNA methylation maintenance and a conserved inhibitory mechanism from DNA demethylation in chickens and mammals.
Journal Genes Genomics
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.
Volume 43(3)
Pages 269-280
Published 2021-3-1
DOI 10.1007/s13258-021-01046-7
PII 10.1007/s13258-021-01046-7
PMID 33555502
PMC PMC7966644
MeSH Animals Cell Line, Tumor Cells, Cultured Chickens / genetics Chromatin DNA Demethylation* DNA Methylation* DNA Modification Methylases / metabolism Dioxygenases / metabolism Female Humans Induced Pluripotent Stem Cells / metabolism Mice Mouse Embryonic Stem Cells / metabolism
Chicken / Quail WL-G