論文

国際誌
2021年1月29日

The Temporal Order of DNA Replication Shaped by Mammalian DNA Methyltransferases.

Cells
  • Shin-Ichiro Takebayashi
  • ,
  • Tyrone Ryba
  • ,
  • Kelsey Wimbish
  • ,
  • Takuya Hayakawa
  • ,
  • Morito Sakaue
  • ,
  • Kenji Kuriya
  • ,
  • Saori Takahashi
  • ,
  • Shin Ogata
  • ,
  • Ichiro Hiratani
  • ,
  • Katsuzumi Okumura
  • ,
  • Masaki Okano
  • ,
  • Masato Ogata

10
2
記述言語
英語
掲載種別
研究論文(学術雑誌)
DOI
10.3390/cells10020266

Multiple epigenetic pathways underlie the temporal order of DNA replication (replication timing) in the contexts of development and disease. DNA methylation by DNA methyltransferases (Dnmts) and downstream chromatin reorganization and transcriptional changes are thought to impact DNA replication, yet this remains to be comprehensively tested. Using cell-based and genome-wide approaches to measure replication timing, we identified a number of genomic regions undergoing subtle but reproducible replication timing changes in various Dnmt-mutant mouse embryonic stem (ES) cell lines that included a cell line with a drug-inducible Dnmt3a2 expression system. Replication timing within pericentromeric heterochromatin (PH) was shown to be correlated with redistribution of H3K27me3 induced by DNA hypomethylation: Later replicating PH coincided with H3K27me3-enriched regions. In contrast, this relationship with H3K27me3 was not evident within chromosomal arm regions undergoing either early-to-late (EtoL) or late-to-early (LtoE) switching of replication timing upon loss of the Dnmts. Interestingly, Dnmt-sensitive transcriptional up- and downregulation frequently coincided with earlier and later shifts in replication timing of the chromosomal arm regions, respectively. Our study revealed the previously unrecognized complex and diverse effects of the Dnmts loss on the mammalian DNA replication landscape.

リンク情報
DOI
https://doi.org/10.3390/cells10020266
PubMed
https://www.ncbi.nlm.nih.gov/pubmed/33572832
PubMed Central
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7911666
ID情報
  • DOI : 10.3390/cells10020266
  • PubMed ID : 33572832
  • PubMed Central 記事ID : PMC7911666

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