Extended Data Fig. 5: Direct target genes of TFAP2C, SOX17 and PRDM1.

a, Genomic distribution of the TFAP2C peaks in hPGCLC aggregates⁴⁶. b, Cumulative distribution function plot showing the functional prediction of TFAP2C. The TFAP2C peaks were assigned to genes with TSS within 100 kb of the peak summits. A regulatory potential score was calculated for each gene based on the distance between the peak summit and the TSS⁹⁶. The genes were then divided into three groups (upregulated, downregulated and unchanged) according to their expression patterns in TFAP2C KO day2 hPGCLCs versus the wild-type control²⁰. Cumulative distribution function plot was generated for each group with genes ranked by decreasing regulatory potential. A one-tailed Kolmogorov-Smirnov test was used to determine the statistical significance between the differentially expressed groups and the unchanged group. c, The enrichment of TFAP2C, SOX17 and PRDM1 peaks in genomic loci that gained ATAC, H3K4me1, H3K4me3, H3K27ac or H3K27me3 signals during the PreME to hPGCLC transition. The TF peaks were categorized into seven cooperativity classes as in Fig. 4a. The dot size represents the fraction of chromatin peaks that overlapped with the TF peaks. Dot color indicates enrichment significance. d, Alluvial plots showing the enhancer (upper panel) and promoter (lower panel) state transition from PreME to hPGCLC. The enhancers/promoters that became active/inactive in hPGCLCs were used for TF binding enrichment analysis in Fig. 4b. e, Venn diagram showing the intersection of upregulated and downregulated genes in SOX17, TFAP2C and PRDM1 KO hPGCLCs/aggregate²⁰. Upregulated and downregulated genes were defined as (log2(fold change versus wild-type control) >1 and adjusted p-value < 0.05) and (log2(fold change versus wild-type control) <(-1) and adjusted p-value < 0.05), respectively. f, The number of direct up and down target genes of TFAP2C, SOX17 and PRDM1 based on their cooperative binding. g, Enrichment of chromatin remodelling factor binding sites in TFAP2C, SOX17 and PRDM1 peaks in hPGCLCs. The y-axis shows the chromatin remodelling factors that were amongst the top 10 enriched transcriptional regulators (ReMap2020) in any of the five peak sets (x-axis).