Programming asynchronous replication in stem cells

Hagit Masika, Marganit Farago, Merav Hecht, Reba Condiotti, Kirill Makedonski, Yosef Buganim, Tal Burstyn-Cohen, Yehudit Bergman*, Howard Cedar

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

7 Scopus citations

Abstract

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.

Original languageAmerican English
Pages (from-to)1132-1138
Number of pages7
JournalNature Structural and Molecular Biology
Volume24
Issue number12
DOIs
StatePublished - 2017

Bibliographical note

Publisher Copyright:
© 2017 Nature America, Inc.

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