Programming asynchronous replication in stem cells

Nat Struct Mol Biol. 2017 Dec;24(12):1132-1138. doi: 10.1038/nsmb.3503. Epub 2017 Nov 13.


Many regions of the genome replicate asynchronously and are expressed monoallelically. It is thought that asynchronous replication may be involved in choosing one allele over the other, but little is known about how these patterns are established during development. We show that, unlike somatic cells, which replicate in a clonal manner, embryonic and adult stem cells are programmed to undergo switching, such that daughter cells with an early-replicating paternal allele are derived from mother cells that have a late-replicating paternal allele. Furthermore, using ground-state embryonic stem (ES) cells, we demonstrate that in the initial transition to asynchronous replication, it is always the paternal allele that is chosen to replicate early, suggesting that primary allelic choice is directed by preset gametic DNA markers. Taken together, these studies help define a basic general strategy for establishing allelic discrimination and generating allelic diversity throughout the organism.

MeSH terms

  • Adult Stem Cells / cytology*
  • Alleles
  • Animals
  • Cell Line
  • Cell Proliferation / genetics*
  • DNA Methylation / genetics
  • DNA Replication / genetics*
  • Embryonic Stem Cells / cytology*
  • Genetic Markers / genetics
  • Genomic Imprinting / genetics*
  • Mice


  • Genetic Markers