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

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 organism. Using mouse embryonic stem cells as a model system, we demonstrate that the binding of an RNA polymerase complex on DNA prior to 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 is 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. Overall design: ChIP-seq of H3K4me3 in ICM and ChIP-seq of H3K4me3 and RNAP II in ES cells and TKO cells