Gene

Biology

Statistics

DNA replication

Stem cell

Somatic cell

Genetics

Replication timing

Mathematics

Embryonic stem cell

Allele

Replicate

Nature Structural & Molecular Biology

Asynchronous replication-timing patterns undergo programmed switching between maternal and paternal alleles in embryonic and adult stem cells. 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.

Programming asynchronous replication in stem cells