Fig. 4: scNOMeRe-seq reveals a ZGA associated regulome.

a, b Volcano plot showing the weighted Pearson correlations between chromatin accessibility of promoter-NDRs (a) / distal-NDRs (b) and the expression level of corresponding ZGA genes across cells from zygote to 2-cell stage. Significant associations (FDR < 0.1) are in red (positive) and blue (negative). The number of CREs and unduplicated genes are labeled. c, d Heat map showing the enrichment of ZGA associated CREs in repeats (c) and histone modifications (d) (refs. ^7,8,9) of early embryos. e TF motifs identified from ZGA associated CREs. Only TFs with the P-value <1 × 10⁻¹⁰ and TPM ≥ 5 at least at one stage were included. P-value, binomial test in HOMER. f Heat map showing the TF activity (left) and expression level (right) of ZGA enriched TFs in each individual cell of zygote and 2-cell embryos. g Scatter plot showing the difference of TF activity (left) and expression level (right) between zygote and 2-cell stage. The genes labeled in red indicate the TFs showing significantly differential activity (left, FDR < 0.1) or expression level (right, FDR < 0.01). h Volcano plot showing the Pearson correlations between TF activity and expression level across cells from zygote to 2-cell stage. Significantly correlated (FDR < 0.1) TFs that enriched in ZGA associated CREs and showed higher TF activities and expression level in 2-cell embryos are labeled. i Scatter plot showing TF activity and expression level of Rarg, Nr5a2 and Klf4 in each single cell of zygote and 2-cell embryos. The corresponding enriched DNA-binding motifs are shown at the bottom of each TF. j A model showing ZGA process regulated by multiple epigenetic layers, transcription factors and repeat elements. The sample size of each group is provided in Supplementary Fig. 3g. Source data for e are provided as a Source Data file.