論文

査読有り 国際誌
2019年9月

Single-cell DNA replication profiling identifies spatiotemporal developmental dynamics of chromosome organization.

Nature genetics
  • Hisashi Miura
  • ,
  • Saori Takahashi
  • ,
  • Rawin Poonperm
  • ,
  • Akie Tanigawa
  • ,
  • Shin-Ichiro Takebayashi
  • ,
  • Ichiro Hiratani

51
9
開始ページ
1356
終了ページ
1368
記述言語
英語
掲載種別
研究論文(学術雑誌)
DOI
10.1038/s41588-019-0474-z

In mammalian cells, chromosomes are partitioned into megabase-sized topologically associating domains (TADs). TADs can be in either A (active) or B (inactive) subnuclear compartments, which exhibit early and late replication timing (RT), respectively. Here, we show that A/B compartments change coordinately with RT changes genome wide during mouse embryonic stem cell (mESC) differentiation. While A to B compartment changes and early to late RT changes were temporally inseparable, B to A changes clearly preceded late to early RT changes and transcriptional activation. Compartments changed primarily by boundary shifting, altering the compartmentalization of TADs facing the A/B compartment interface, which was conserved during reprogramming and confirmed in individual cells by single-cell Repli-seq. Differentiating mESCs altered single-cell Repli-seq profiles gradually but uniformly, transiently resembling RT profiles of epiblast-derived stem cells (EpiSCs), suggesting that A/B compartments might also change gradually but uniformly toward a primed pluripotent state. These results provide insights into how megabase-scale chromosome organization changes in individual cells during differentiation.

リンク情報
DOI
https://doi.org/10.1038/s41588-019-0474-z
PubMed
https://www.ncbi.nlm.nih.gov/pubmed/31406346
ID情報
  • DOI : 10.1038/s41588-019-0474-z
  • PubMed ID : 31406346

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