Role of transcription complexes in the formation of the basal methylation pattern in early development

Razi Greenfield, Amalia Tabib, Ilana Keshet, Joshua Moss, Ofra Sabag, Alon Goren, Howard Cedar*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

12 Scopus citations

Abstract

Following erasure in the blastocyst, the entire genome undergoes de novo methylation at the time of implantation, with CpG islands being protected from this process. This bimodal pattern is then preserved throughout development and the lifetime of the organism. Using mouse embryonic stem cells as a model system, we demonstrate that the binding of an RNA polymerase complex on DNA before de novo methylation is predictive of it being protected from this modification, and tethering experiments demonstrate that the presence of this complex is, in fact, sufficient to prevent methylation at these sites. This protection is most likely mediated by the recruitment of enzyme complexes that methylate histone H3K4 over a local region and, in this way, prevent access to the de novo methylation complex. The topological pattern of H3K4me3 that is formed while the DNA is as yet unmethylated provides a strikingly accurate template for modeling the genomewide basal methylation pattern of the organism. These results have far-reaching consequences for understanding the relationship between RNA transcription and DNA methylation.

Original languageAmerican English
Pages (from-to)10387-10391
Number of pages5
JournalProceedings of the National Academy of Sciences of the United States of America
Volume115
Issue number41
DOIs
StatePublished - 9 Oct 2018

Bibliographical note

Funding Information:
ACKNOWLEDGMENTS. This research was supported by grants from the European Research Council, the Israel Science Foundation, and the Israel Cancer Research Fund.

Publisher Copyright:
© 2018 National Academy of Sciences.All Rights Reserved.

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