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. 2021 Feb 19;31(5):526–541. doi: 10.1038/s41422-021-00477-x

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© The Author(s) 2021

Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/.

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Fig. 5 — a Heatmaps showing H3K4me3/H3K27me3 enrichment at all promoters of genes (± 2.5 kb) in naïve mESCs, EpiLCs, EpiSCs, fPSCs, E6.5 epiblast and recently reported RSCs, FTW-ESCs as well as FS-AXR. The intensity of H3K4me3/H3K27me3 was normalized as RPKM. The data of H3K4me3/H3K27me3 for naïve mESCs, EpiLCs, EpiSCs, RSCs, FTW-ESCs, FS-AXR, and E6.5 epiblast were obtained from the published resources.^{42–44,56,57} b Average plot showing H3K4me3 enrichment at all loci of super-bivalent, housekeeping, and bivalent genes in naïve mESCs, EpiLCs, EpiSCs, RSCs, FTW-ESCs, FS-AXR, fPSCs, and E6.5 epiblast. The H3K4me3 enrichment at super bivalent and bivalent genes was normalized to the average intensity of housekeeping genes in each cell line. c Scatter plots displayed the enrichment of H3K4me3 and H3K27me3 of 3992 bivalent genes in different cell types. The average H3K4me3 enrichment of housekeeping genes (HK. ave) was shown for each of cell types. The blue lane indicate an arbitrary cutoff of H3K27me3 for each stage (normalized RPKM > 1). Super-bivalent and bivalent genes were shown as red and gray, respectively. The number of super-bivalent genes (right top) was shown in naïve mESCs, EpiLCs, EpiSCs, RSCs, fPSCs, FTW-ESCs, FS-AXR, and E6.5 epiblasts. d UCSC Genome Browser views showing H3K4me3 enrichment at the locus of super-bivalent genes (Hoxa cluster, Gata4, and Pax2) and housekeeping gene (Rpn1) in mESCs, EpiLCs, EpiSCs, RSCs, FTW-ESCs, FS-AXR, fPSCs, and E6.5 epiblast. e Hierarchical clustering analysis of DNA methylation for naïve mESCs, EpiLCs, fPSCs, EpiSCs and E5.5/6.5/7.5 epiblasts.^58–61 f Smoothed scatter plot of genome-wide DNA methylation between EpiLCs or fPSCs and E5.5, or E6.5 epiblasts. Density of data pointed the ranges from blue (low) to green (intermediate) and yellow (high). g Genome Browser views showing the DNA methylation and H3K4me3/H3K27me3 enrichment at the promoters of selected formative markers (Otx2, Zic5) in naïve mESCs, EpiLCs, and EpiSCs, as well as fPSCs and E6.5 epiblasts. h Snapshots of DNA methylation and enrichment of H3K4me3 and H3K27me3 at the promoters of selected germ-layer markers (Pax6, Foxf1 and Foxa2) and Oct4 in naïve mESCs, EpiLCs, and EpiSCs, as well as fPSCs and E6.5 epiblasts.