SCIENCE@home

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

Razi Greenfield,A. Tabib,I. Keshet,J. Moss,O. Sabag,A. Goren,H. Cedar

Published 2018 in Proceedings of the National Academy of Sciences of the United States of America

ABSTRACT

Significance This paper reveals the molecular logic for generating the basal methylation pattern in each individual following erasure of the gametic profile in the preimplantation embryo. The results show that transcription factors and the RNA polymerase complex play a major role in protecting recognized regions from de novo methylation by recruiting the H3K4 methylation machinery. Because methylation is stably maintained through development, this mechanism serves to perpetuate the activity state present in the early embryo. This model may also help explain how transient factors from the gametes may influence methylation patterns in the offspring and, thereby, contribute to intergenerational epigenetic inheritance. 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 genome-wide basal methylation pattern of the organism. These results have far-reaching consequences for understanding the relationship between RNA transcription and DNA methylation.

PUBLICATION RECORD

CITATION MAP

EXTRACTION MAP

CLAIMS

  • No claims are published for this paper.

CONCEPTS

  • No concepts are published for this paper.

REFERENCES

Showing 1-47 of 47 references · Page 1 of 1

CITED BY

Showing 1-19 of 19 citing papers · Page 1 of 1