Fig. 1: CBP/P300 activity is essential for activation of developmental genes but dispensable for activation of housekeeping genes during ZGA.

A Schematic showing the mechanism of CBP/P300 inhibitors. B Schematic showing CBP/P300 inhibitor treatment in medaka. C Phenotypes of embryos at 1 dpf. Magenta dashed lines indicate the location of cells. DMSO-treated embryos formed embryonic bodies normally, while others did not. D Representative Western blot of GAPDH and H3K27ac in DMSO (DM) or A485-treated medaka embryos. Linearity was tested using titrated samples from the wild type (WT) embryos. Same number of embryos (1×) were loaded to lanes. E Western blot of GAPDH and H3K27ac in SGC-CBP30-treated embryos. Linearity was tested using DMSO (DM)-treated embryos. Same number of embryos (1×) were loaded to lanes. F Quantification of (D). Each dot indicates the intensity of H3K27ac band normalized to GAPDH intensity. Two-sided Welch’s t test against DMSO. n = 3 biological replicates. Source data are provided as a Source Data file. G Quantification of (E). Each dot indicates the intensity of H3K27ac band normalized to GAPDH intensity. Two-sided unpaired Student’s t test. n = 3 biological replicates. Source data are provided as a Source Data file. H Scatter plots indicate RNA-seq expression levels in DMSO and 20 µM A485-treated embryos. Red and blue dots indicate significantly upregulated and downregulated genes ( | log2 fold change | > 1, adjusted p value < 0.01, RPKM > 1.5) in A485-treaed embryos, respectively. Pink, green, and light blue dots indicate Maternal, Maternal-ZGA, and Pure ZGA genes (see Supplementary Fig. 1F–H), respectively. n = 2 biological replicates. I Scatter plots indicate RNA-seq expression levels in DMSO and SGC-CBP30-treated embryos. Red and blue dots indicate significantly upregulated and downregulated genes ( | log2 fold change | > 1, adjusted p value < 0.01, RPKM > 1.5) in SGC-CBP30-treated embryos, respectively. Pink, green, and light blue dots indicate Maternal, Maternal-ZGA, and Pure ZGA genes (see Supplementary Fig. 1F–H), respectively. n = 2 biological replicates. J Venn diagram indicates overlap of ZGA genes (see Supplementary Fig. 1E) and significantly downregulated genes in A485 or SGC-CBP30-treated embryos. K Bubble plot indicates the results of GO analysis (FDR < 0.05, fold enrichment >2, top 10 GO terms). L Heatmap showing expression level of representative developmental genes. RNA-seq data of normal embryos¹⁹ and DMSO- or A485-treated embryos in this study are shown. M Heatmap showing RNA-seq transcript enrichment around TSS (bottom) and its average (top). *: p < 0.05, **: p < 0.01, ***: p < 0.001, NS: not significant. dpf /hpf: days/hours post fertilization. Error bars indicate the mean ± s.d.