GSE124342
Hi-C of WT E14 mouse ES cells grown in serum and 2i media
Dynamic reprogramming of global DNA methylation impacts on the genomic deposition of the Polycomb-mediated repressive histone mark H3K27me3. DNA hypomethylation in ground state embryonic stem cells (ESCs) results in a reversible redistribution of H3K27me3 from its normal target loci. Thus, a signalling induced shift of ESCs to ground state results in both DNA methylation and Polycomb patterns that are quite distinct from their primed counterparts. Here we investigated the impact of DNA methylation directed Polycomb redistribution on higher-order chromatin structure in the ground state. Using a targeted single-locus approach (FISH) we can demonstrate local decompaction at Hox loci in the ground state, which is consistent with genome-wide data (Hi-C) indicating that chromatin structure is globally altered in ground state relative to primed ESCs. Polycomb targets are similarly decompacted in hypomethylated E3.5 mouse blastocysts. ESC lines which maintain a high level of DNA methylation in ground state show no decompaction at Hox loci. Our results suggest that DNA-methylation mediated reprogramming of Polycomb binding drives higher order chromatin organisation in stem cells and early development. Overall design: In situ Hi-C experiments on E14 mESCs in serum and 2i culture with two replicates per condition