Dynamic and static maintenance of epigenetic memory in pluripotent and somatic cells.

Zohar Shipony*, Zohar Mukamel, Netta Mendelson Cohen, Gilad Landan, Elad Chomsky, Shlomit Reich Zeliger, Yael Chagit Fried, Elena Ainbinder, Nir Friedman, Amos Tanay

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

113 Scopus citations


Stable maintenance of gene regulatory programs is essential for normal function in multicellular organisms. Epigenetic mechanisms, and DNA methylation in particular, are hypothesized to facilitate such maintenance by creating cellular memory that can be written during embryonic development and then guide cell-type-specific gene expression. Here we develop new methods for quantitative inference of DNA methylation turnover rates, and show that human embryonic stem cells preserve their epigenetic state by balancing antagonistic processes that add and remove methylation marks rather than by copying epigenetic information from mother to daughter cells. In contrast, somatic cells transmit considerable epigenetic information to progenies. Paradoxically, the persistence of the somatic epigenome makes it more vulnerable to noise, since random epimutations can accumulate to massively perturb the epigenomic ground state. The rate of epigenetic perturbation depends on the genomic context, and, in particular, DNA methylation loss is coupled to late DNA replication dynamics. Epigenetic perturbation is not observed in the pluripotent state, because the rapid turnover-based equilibrium continuously reinforces the canonical state. This dynamic epigenetic equilibrium also explains how the epigenome can be reprogrammed quickly and to near perfection after induced pluripotency.

Original languageAmerican English
Pages (from-to)115-119
Number of pages5
Issue number7516
StatePublished - 2014
Externally publishedYes

Bibliographical note

Funding Information:
Acknowledgements We thank E. Kenigsberg, E. Yaffe and the Tanay group for discussions. Research in the Tanay group was supported by the European Research Council (EVOEPIC), the EU BLUEPRINT project, the Israel Science Foundation (1050/ 12 and I-Core) the Israel Ministry of Science and the Helen and Martin Kimmel Award.


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