CHD8 is essential for suppressing P53 signaling in HSPCs. (A) Heat maps for ATAC-seq peaks from WT and Chd8^−/− LSKs showing ±1.5 kb around the ATAC-seq peak center. Results are from 2 biological replicates. WT represents Chd8^F/F mice. (B) Tag enrichment of accessible genomic regions relative to ATAC-seq peaks. Results are from 2 biological replicates. (C) Western blot of histone modification markers in WT and Chd8^−/− HSPCs. (D) PCA plot of RNA-seq data from WT and Chd8^−/− LSKs. (E) Differential expression of transcripts between WT and Chd8^−/− LSKs. Log₂-fold change >1.0; P < .05. (F) KEGG enrichment of DEGs from RNA-seq showed increased P53 signaling after loss of CHD8, using DAVID (Database for Annotation, Visualization, and Integrated Discovery). (G) Heat map of differentially expressed P53 downstream genes between WT and Chd8^−/− LSKs. (H) RT-PCR of selective P53 target genes in WT and Chd8^−/− LSKs and SLAM HSCs. The data represent 3 biological replicates. **P < .01; ***P < .001. ns, not significant.