Extended Data Fig. 7: DMS germline genes are derepressed in Nsd1 KO embryos.
From: Reprogramming of H3K36me2 guides lineage-specific post-implantation de novo DNA methylation
a, Volcano plots showing gene expression changes in E6.5 Nsd1 KO Epi and ExE. Differentially expressed genes (DEGs), adjusted p-value < 0.05, fold change ≥ 2. GO terms for down-regulated and up-regulated genes are also shown. b, Scatter plots comparing DNA methylation changes at promoters (TSS ± 500 bp) and gene expression changes between E6.5 Nsd1 KO and control embryos in Epi or ExE. Black dots, DNA methylation-sensitive (DMS) germline genes. Representative DMS genes are labeled. c, Box plots showing the transcription (RNA) of CGI and non-CGI DMS germline genes in control and Nsd1 KO embryonic and extra-embryonic lineages, and H3K36me2 at CGI and non-CGI promoters of DMS germline genes. All CGI and non-CGI genes are similarly analyzed as controls (‘All’). Center line, median; box, 25th and 75th percentiles; whiskers, 1.5 × IQR. P = 3e-9 and P = 2e-7 for Ctrl vs. Nsd1 KO Em lineages for DMS CGI genes at E6.5 and E8.5, respectively; P < 2e-308 for Ctrl vs. Nsd1 KO Em lineages for all CGI genes both at E6.5 and E8.5; P = 2e-12 and P = 6e-8 for Ctrl vs. Nsd1 KO Em lineages for DMS non-CGI genes at E6.5 and E8.5, respectively; P = 4e-215 and P = 4e-4 for Ctrl vs. Nsd1 KO Em lineages for all non-CGI genes at E6.5 and E8.5, respectively; P = 6e-3 and P = 5e-4 for Ctrl vs. Nsd1 KO Ex lineages for DMS CGI genes at E6.5 and E8.5, respectively; P = 0.27 and P = 2e-100 for Ctrl vs. Nsd1 KO Ex lineages for all CGI genes at E6.5 and E8.5, respectively; P = 7e-7 and P = 3e-3 for Ctrl vs. Nsd1 KO Ex lineages for DMS non-CGI genes at E6.5 and E8.5, respectively; P = 8e-87 and P = 1e-34 for Ctrl vs. Nsd1 KO Ex lineages for all non-CGI genes at E6.5 and E8.5, respectively; P = 1e-23, P = 7e-7, P = 6e-11, and P = 1e-3 for DMS vs. all CGI genes in E6.5 Epi, DMS vs. all non-CGI genes in E6.5 Epi, DMS vs. all CGI genes in E6.5 ExE, and DMS vs. all non-CGI genes in E6.5 ExE, respectively (two-sided paired Wilcoxon signed-rank test for RNA, and two-sided Wilcoxon rank-sum test for K36me2). Source numerical data are available in source data.
